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\begin{document}

\title{Case report: Acute Liver failure; An Unusual Complication of Dengue
Fever}



\author[1]{Hafsa Uzair}%
\author[1]{Radeyah  Waseem}%
\author[1]{Naresh Kumar}%
\author[1]{Muhammad Sheheryar  Hussain}%
\author[1]{Hussain Haider Shah}%
\affil[1]{Dow University of Health Sciences}%


\vspace{-1em}



  
  \date{June 16, 2024}


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\selectlanguage{english}
\begin{abstract}
Dengue is one of the most prevalent viral equatorial diseases which has
recently become a major health concern globally. This case report
exemplifies a case of Expanded Dengue Syndrome in 29 years old male who
was received by a Tertiary Care Hospital in Karachi and expired due to
liver failure.%
\end{abstract}%



\sloppy


\textbf{Title: Acute Liver failure: An Unusual Complication of Dengue
Fever}

\textbf{Article Type:} Case report

\textbf{}

Abstract

Dengue fever is one of the most prevalent viral equatorial diseases
which has recently become a major health concern globally. The disease
stems from a single-stranded positive RNA virus, which belongs to the
family Flaviviridae, genus flavivirus. The disease is characterized by
fever along with two of the following associated symptoms; (1)
headaches, (2) myalgias, (3) leukopenia, and (4) rash. Plasma leakage is
also a usual finding and its progress manifests as either compensated,
or uncompensated shock. The shock syndrome may confer lethality by
causing multi-organ failure or death. The term Expanded Dengue Syndrome
(EDS) was coined by WHO in 2012 when the clinical presentation became
vague and showed generalized impacts on normal physiology which could
not be confined to a specific clinical spectrum. It amalgamates the
findings exacerbating from the usual clinical picture and manifesting as
an unusual presentation. Liver involvement is among the mainstay
features of DF. Liver injury in DF is usually manifested by nausea,
vomiting, abdominal discomfort, and anorexia concurrent with the
findings of hepatomegaly and elevated serum transaminase levels.
Laboratory parameters including a mean Platelet count \textless{}
20,000/mm, Aspartate Transaminase Levels \textgreater{} 45 IU, and
lymphocytes \textless{} 1500 were significantly associated with severe
disease. This case report exemplifies a case of Expanded Dengue Syndrome
in 29 years old male who was received by a Tertiary Care Hospital in
Karachi and expired after a week secondary to liver failure.

Introduction

Dengue fever is one of the most prevalent viral equatorial diseases
which has recently become a major health concern globally. The disease
stems from a single-stranded positive RNA virus, which belongs to the
family Flaviviridae, genus flavivirus. The Dengue Virus has four
identified serovars labeled as DENV-1, DENV-2, DENV-3, and DENV-4 and is
transmitted by the vector, female Aedes Mosquito, particularly Aedes
aegypti and Aedes albopictus~{[}1{]}. It is now endemic in more a than
hundred countries including The Americas, South-East Asia, and Western
Pacific regions~{[}2{]}.

Dengue virus has an incubation period of 3-7 days, followed by symptoms
that can appear in three distinct phases; febrile phase (2-7 days and
persists throughout the illness), critical phase (3-7 days when the
disease may disseminate and involve further organ systems), and finally
the convalescent, or recovery phase~{[}3{]}.

The disease is characterized by fever along with two of the following
associated symptoms; (1) headaches, (2) myalgias, (3) leukopenia, and
(4) rash~{[}3{]}. Dengue hemorrhagic fever (DHF) is among the clinically
complicated pictures which may present with a severe fever, hemorrhage
with or without hepatosplenomegaly, and occasionally circulatory
failure~{[}1{]}. Dengue Shock Syndrome (DSS) is another variant
characterized by hypotension and accompanying chills and
agitation~{[}4{]}. The term Expanded Dengue Syndrome (EDS) was coined by
WHO in 2012 when the clinical presentation became vague and showed
generalized impacts on normal physiology which could not be confined to
a specific clinical spectrum~{[}5{]}.

Liver involvement is among the mainstay features of DF~{[}3{]}. Dengue
virus blunts the physiologic hepatic functioning by diverse mechanisms
involving direct disruption of hepatocytes and Kupffer cell function,
and indirectly by impairment of the immune system via a cytokine surge
mediated by t-cells and circulatory failure causing ischemic liver
injury~{[}6{]}. Liver injury in DF is usually manifested by nausea,
vomiting, abdominal discomfort, and anorexia concurrent with the
findings of hepatomegaly and elevated serum transaminase levels~{[}7{]}.

A recent outbreak of DF occurred in Pakistan starting from 1st January
to 27th September 2022, with around 25,932 people being afflicted and 62
deaths reported by the National Institute of Health in
Islamabad~{[}8{]}.

Case Presentation

A 29-year-old Pakistani male was presented to the Emergency Department
of a Tertiary Care Hospital in Karachi on 19th October 2022 with altered
level of consciousness for 1 day and a history of fever, vomiting, and
abdominal pain for the past 5 days.

On history, the fever was reported to be high-grade (maximum spike of
104*F), with rigors and chills, intermittent with a peak after every
twelve hours. Vomiting was described as projectile, occurring three to
four times a day, watery, and not blood-stained. Abdominal pain was
localized to the right hypochondriac regions, with no shifting or
radiations. It was described as an aching, intense pain that aggravated
after vomiting and was not~relieved despite the administration of
analgesics. He then gradually developed an altered loss of consciousness
which initiated with irrelevant conversation and progressively worsened.
The patient was under hospital care for 4 days before being referred to
the current set-up after behavioral alterations were evident. His viral
markers~for Hepatitis A~,B and hepatitis E infection were negative,
Dengue Antigen and Malaria parasite were also negative on 17th October
2022. A chest X-Ray was also performed (Figure~\emph{1}).\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

\textbf{Figure~1: Chest X-ray dated 17th October showing bilateral
pleural effusion}

Upon receiving the patient in the Emergency Department, pulse and blood
pressure were recorded as 63 beats/minute and 94/50 mmHg, and he was
physically assaulting family and staff members alike along with
displaying resistance to therapeutic care by removing cannulas and
nasogastric tubes; he also showed impedance to taking medicine. On
evaluation by the Psychiatry Department, he was under the impression of
delirium. The Laboratory investigations conducted are reported in
Table~\emph{1}, which evidently reports deranged Liver Function Test
values. The patient was injected with one liter of Ringer's Lactate to
stabilize his vitals and was then advised admission to the Medical HDU.

The patient was received in Medical HDU in a drowsy state (not oriented)
and on repeated examination, vitals were as noted: Pulse- 66
beats/minute, Blood Pressure- 130/80 mmHg, and respiratory rate- 24
breaths/minute. The abdomen was examined to be flat with the umbilicus
centrally placed and inverted, with the lower edge of the liver palpable
1 cm below the costal margin with moderate tenderness in right
hypochondrium, no splenomegaly appreciated ,signs of free fluid present
with positive shifting dullness Pupils were found to be equally reactive
to light bilaterally .

The patient was shifted to Medical ICU on 20th October 2022 with the
Laboratory findings described in Table~\emph{1}~and being treated along
the lines of Fulminant Liver Failure. The progressive fluctuations in
hemoglobin levels, Total Leukocyte count, Platelets count, and
electrolyte levels since before and during admission in the ICU are
tabulated in Table~\emph{1}.

The patient was subjected to the treatment regimen, which included
Meropenem 1 gm IV x TDS, Risek 40 mg IV x OD,~N-acetylcysteine 150 mg/kg
in 5 divided doses Loading dose of 150mg/kg in 100ml 5\% dextrose water
over 15 minutes with the maintenance dose of 12.5 mg/kg/hour over 4
hours and third dose of 6.25 mg/kg/hour over 16 hours, Mannitol 200 ml
IV stat then 100 ml IV x OD (3 days) and syrup Duphalac 30 ml BD

The patient tested positive for Dengue IgM Antibody and an Ultrasound of
the whole abdomen was concurrently performed on 22nd October, with the
findings as follows-

\selectlanguage{ngerman}·~Liver - Normal in size measuring 15.1 cm with irregular outline and
decreased parenchymal echogenicity. The portal vein was 1.0 cm, while
the intrahepatic duct and vessels showed no abnormality. No focal mass
was visualized.

·~Gall-bladder - A thick, hypoechoic wall measuring 1.0 cm was
conceived. There were no mass or calculi apprehended, and the common
bile duct was found to be 0.4 cm in diameter. The findings were denoted
as acute acalculous cholecystitis.

·~No abnormal finding was reported in the pancreas and spleen.

·~Kidneys - Bilaterally normal in size, shape, and position.
Bilaterally, renal parenchymal changes were observed.

·~General - Gross ascites was evident, bilateral gross pleural effusion
secondary to lung collapse.

The patient became tachypnic and tachycardic with drop in GCS due to
which patient was electively intubated on~21st October 2022. The patient
gradually developed scrotal swelling which was evaluated by the Urology
Department on 26th October 2022. The department commented on the patient
having generalized body swelling which was predisposed to scrotal
swelling. The patient was currently on a mechanical ventilator and
required only scrotal support and elevation for relief. However, he
developed an abnormal breathing rhythm which was found secondary to
blockage of the endotracheal tube with blood clots signifying massive
internal hemorrhage. 4 packs of Fresh Frozen Plasma (FFP), 6 packs of
platelets, and 1 bag of Packed Cell Volume (PCV) was transfused to
combat the deteriorating hemodynamics of the patient.

The patient succumbed to the disease at 10:18 A.M. on 27th October
secondary to cardiopulmonary arrest as a complication of acute and
subacute liver failure.

Discussion

Dengue is typically reported to the clinical setting with a history of
high grade fever, and drastically depleting platelets. Plasma leakage is
also a usual finding and its progress manifests as either compensated,
or uncompensated shock. The shock syndrome may confer lethality by
causing multi-organ failure or death. The term `Expanded Dengue
Syndrome' amalgamates the findings exacerbating from the usual clinical
picture and manifesting as an unusual presentation~{[}9{]}.

Liver involvement is prevalent among people infected with Dengue virus,
most commonly founded in the form of elevated transaminase levels.
Escalating levels of serum glutamic-oxaloacetic transaminase and serum
glutamic-pyruvic transaminase are in corollary to disease severity and
are indirectly proportional to platelet counts~{[}10{]}. Concomitant
complains of abdominal pain, anorexia, nausea and vomiting are strong
indicators of liver involvement in a diagnosed dengue patient~{[}11{]}.

A myriad of factors contributes towards liver involvement constituting
direct damage and loss of hepatocytes, and indirect damage mediated by
the host immune system which jeopardizes vascular and circulatory
integrity and may also exhibit metabolic dysfunction such as acidosis
and hypoxia~{[}12{]}. Certain chemokines such as Interleukin 17 and
Interleukin 10 (IL-17, IL-10) are also implicated in cases of severe
hepatic involvement in the absence of prominent fluid leakage and
endothelial damage, where immune mediators are expected to be
involved~{[}13{]}.

According to a study conducted by Jayaratne et al., the presentation of
abdominal pain, vomiting, clinical fluid accumulation, and mucosal
bleeding was persistently high in Dengue patients who developed severe
disease. Laboratory parameters including a mean Platelet count
\textless{} 20,000/mm, Aspartate Transaminase Levels \textgreater{} 45
IU, and lymphocytes \textless{} 1500 were significantly associated with
severe disease~{[}14{]}.

Conclusions

Our case emphasizes the lethality of Dengue fever and its complications
when the case is bought into clinical attention once hepatic
encephalopathy has developed. Infection by Dengue Virus was proven
practically days after signs and symptoms developed which was
significantly contributory factor towards the poor outcome in this
patient. Fulminant Hepatic Failure ensued with significant capillary
leak and overt bleeding which manifested acutely before the patient
expired.

References

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\tightlist
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