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Original Article
Hepatic dysfunction is frequent in varicella Infection
Ali Hassan Abro, Ahmed MS Abdou, Abdulla M Ustadi, Hina Syeda Hussaini, Nadeem
Younis Javeed, Ahmed Alhaj Saleh, Dujana A Hamed,
From Infectious Diseases Unit, Rashid Hospital Dubai, United Arab Emirates.
Correspondence: Dr. Ali Hassan Abro. Ward-17. Rashid Hospital Dubai, UAE. 4545
Mob: 00971504741939.Tel: 0097143346651. Email: momal65@hotmail.com
Received: June 2, 2008 Accepted: July 1, 2008
ABSTRACT
Objective: To determine frequency and severity of hepatic dysfunction in adult
chickenpox patients admitted in our hospital.
Material and Methods: This was a hospital based descriptive study conducted from
January 2005 to December 2007 at the Infectious Diseases Unit, Rashid hospital Dubai,
UAE. The demographics, clinical information, radiological and biochemical changes
observed in each patient were entered in a proforma. Full blood count, liver function
tests, blood sugar, urea and electrolytes were done for all the patients, whereas, patients
with clinical and/or biochemical evidence of hepatic dysfunction were subjected to viral
hepatitis serology, coagulation profile, blood culture and ultrasound abdomen.
Management was done as per standard guidelines for the management of chickenpox and
its complications.
Results: A total of 105 patients were entered into the study. Serum alanine transaminases
(ALT) levels were above the reference range in 50.9%. Among the 52 patients with
raised serum ALT levels, 16 (30.7%) had levels >3 times, 4 (7.6%) had >5 times and 5
(9.6%) had >10 times of normal levels. Serum bilirubin was increased above the normal
value in 20% and was greater than 3-folds in 4.9%. High frequency of thrombocytopenia
(p<0.009), pneumonia (p0.004), impaired renal function (p<0.01) and disturbed
coagulation profile (p<0.01) were observed in patients with hepatic dysfunction. Overall,
five (4.9%) patients expired and two (1.9%) of them had acute fulminant hepatic failure.
Conclusion: We observed that liver is frequently involved in adult chickenpox patients
and the severity of hepatic dysfunction ranges from mild elevation of transaminases
levels to acute fulminant hepatic failure. (Rawal Med J 2008;33:201-204).
Key words: Hepatic dysfunction, varicella, adults, ALF.
INTRODUCTION
Chickenpox (Varicella) is a common, usually benign exanthamatous disease caused by
Varicella-Zoster virus, which primarily affects children.
1
Although chickenpox is
common in children, in tropical climate 15-20% cases are reported in adults.
2
Furthermore,
as compared to children the clinical presentation in adults is more severe
and more commonly associated with complications.
3
Common complication of varicella
includes secondary bacterial infection of skin, pneumonia, encephalitis, cerebellar ataxia,
hepatitis, arthritis and glomerulonepheritis.
1
Hepatitis has been described in adults with
varicella infection but is often asymptomatic and limited to mild elevations in the
transaminases.
4
This study was undertaken to determine frequency and severity of hepatic
dysfunction in adult chickenpox patients admitted in our hospital.
PATIENTS AND METHODS
This was a hospital based descriptive study conducted from January 2005 to December
2007 at Infectious Diseases Unit, Rashid Hospital, Dubai, United Arab Emirates
(UAE). Demographics (age, gender, nationality), clinical information, radiological and
biochemical changes observed in each patient were entered in a proforma. The patients
were specifically questioned regarding past medical history of jaundice, medications and
alcohol ingestion. Those with history of chronic liver disease, immunocompromized
(HIV/Drugs), positive viral hepatitis profile, recent intake of hepatotoxic drugs and active
alcohol consumers were excluded from the study.
On admission, full blood count (FBC), liver function test (LFT), blood sugar and urea
electrolytes were performed in all patients, whereas, viral hepatitis serology, coagulation
profile, blood culture and ultrasound abdomen were done in patients with clinical and/or
biochemical evidence of hepatic dysfunction. Management was done as per standard
guidelines for the management of chickenpox and its complications. This consisted of
intravenous acyclovir, antibiotics, intravenous steroids, fresh frozen plasma,
immunoglobulin, ventilator support and hemofiltration depending on patient’s condition.
Statistical analyses included descriptive statistics, bivariate analysis i.e., t-test, chi-square
and Analysis of Variance (ANOVA). A p value of <0.05 was taken as statistically
significant. Data was analyzed by SAS Enterprise Guide 4.1.
RESULTS
A total of 105 patients entered in the study. The mean age was 33.14±9.91years (range
15-65 years) and males outnumbered the females 88 (83.8%) vs 17 (16.2%). Most of the
patients were expatriates who lived or visited the UAE. Out of the 105 patients, 78
(74.2%) were from India and 27 (25.7%) from Pakistan, Srilanka, Philippines and other
countries. The majority of the male patients were laborers who were working in
construction companies, agriculture fields and industries. Most of the patients were living
in labor camps or sharing accommodation and had positive history of contact with
chickenpox patients. Pleomorphic itchy skin rash and fever were the most common
presenting symptoms, whereas, in majority of the patients with significant hepatic
dysfunction, in addition to the above symptoms, also had abdomen pain and vomiting.
Five (4.7%) patients were jaundiced at the time of presentation.
Table 1. Biochemical and Hematological data of Chickenpox patients (n=105)
_____________________________________________________________________
Parameter Pts. with high ALT Pts. with normal ALT P Value
_______________________________________________________________________
ALT 386.98+1249.03 26.83+7.1 U/L 0.03
Albumin 3.86+0.56 3.86+0.78 mg/dl 0.9
Alk Phos. 121.53+82.23 89.22+42.2 U/L 0.03
T.Bilirubin 1.15+0.91 0.71+0.33 mg/dl 0.001
Proth.Time 15.15+2.77 13.46+0.92 sec 0.01
Hemoglobin 15.51+1.54 14.25+1.95 gm/dl. 0.0005
Platelets 149.75+61.99 206.32+135.58x10
3
/ul. 0.009
WBC 9.32+3.84 8.59+4.49x10
3
/ul. 0.3
Urea 35.19+24.64 25.61+12.63 mg/dl. 0.01
_______________________________________________________________________
Out of the 105 patients, 52(50.9%) had raised serum ALT levels above the reference
range with mean ALT levels 218.91±926.1 U/L. Among the 52 patients with raised
serum ALT levels, 16 (30.7%) had levels >3 times, 4 (7.6%) had >5 times and 5 (9.6%)
had >10 times of normal levels. Two patients developed acute hepatic failure and were
managed in ICU. The patients aged 35 years and above had higher incidence of disturbed
liver function tests than those aged less than 35 years (p<0.01). The frequency of hepatic
dysfunction was higher in patients who also developed varicella pneumonia than those
without pneumonia, (p<0.004)
Serum bilirubin, alkaline phosphate, prothrombin time (PT), platelet and urea were
significantly elevated in patients with high ALT (Table 1).
Fig 1. Complications observed in 105 adult chickenpox patients.
50.9
1.9
24.7
2.8
10.4
2.8
41.9
8.5
6.6
27.6
0
10
20
30
40
50
60
Fr
eq
ue
nc
y(
%)
Raised ALT
Enceph/Meningitis
Acute pancreatitis
Skin infection
ARDS
Varicella Pneumoni a
ARF
Septicemia
Acute cholecystitis
Thrombocytopenia
Besides elevated ALT, thrombocytopenia and pneumonia were commonest complication
encountered (Fig. 1). Overall, five (4.7%) patients expired; two of them having acute
hepatic failure complicated by multiple organ failure. The patients who survived, the
serum ALT levels returned to normal limits with in 3-4 weeks in almost all patients.
DISCUSSION
Varicella complications are high in newborns, adults and the immunocompromised
5
and
in males, smokers and pregnant women.
6,7
Varicella infection usually occurs by an air
borne route but it is uncertain whether route of entry is conjunctiva, pharynx or lungs.
8
Viral replication occurs in the regional lymph nodes, lungs, bone marrow, liver, pancreas
and adrenal glands, and this mainly take place in the macrophages.
9
In this case series,
50.9% of the patients had liver damage and 4.9% had transaminase levels in the range of
acute hepatitis, a finding which has been rarely reported. Varicella has been associated
with mild hepatitis but rarely with acute liver failure,
10
whereas, in this study 1.9%
patients developed acute liver failure. Hepatitis in adults with varicella infection has been
reported but is often asymptomatic and limited to mild elevations in the transaminases.
11
In varicella associated hepatic failure, intracellular virions characteristic of herpesviridae
have been demonstrated.
12
The populations at greater risk of developing acute hepatic failure from varicella-zoster
virus are those with either iatrogenic or acquired immunosuppression.
13
However, hepatic
failure secondary to varicella-zoster virus in immunocompetent adult patient from a
tropical country has been reported.
14
In this case series, all the study patients were adult
immunocompetent and were from tropical countries. In this study, we observed that
patients with elevated liver enzymes had high frequency of associated varicella
pneumonia, as reported by others.
15
Varicella-zoster induced hepatic failure and pneumonia carry high mortality.
16,17
The
standard treatment for varicella-zoster infection is Acyclovir, 10mg/kg TDS and this
should be started immediately upon suspicion of the diagnosis. The few patients with
hepatic failure who survived received Acyclovir and/or underwent liver
transplantation.
16,18
Varicella-Zoster immunoglobulin (VZIG) may modify the natural
history of infection but only when administered within 72 hours after exposure.
19
The role
of corticosteroids as adjunctive therapy for the treatment of acute hepatic failure has been
not well studied.
20
In conclusion, we found that liver was frequently involved in adult
chickenpox patients and its severity ranges from mild elevation of serum transaminases
levels to acute fulminant hepatic failure. Furthermore, the patients with hepatic
dysfunction also had high frequency of involvement of the other organs leading to
increased morbidity and mortality rate.
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