1. Isolated Proteinuria in Hepatitis A Versus E Virus
(HAV vs HEV) Infected Patients: A Hospital
Based Observational Study
Corresponding Author:
Dr. Waheeda Nargis, Associate Professor, Department of Biochemistry, Uttara Adhunik Medical College, Dhaka, Bangladesh.
E‑mail: waheedanargis@yahoo.com Original Article
W Nargis1, BU Ahamed2
1Associate Professor, Department of Biochemistry, Uttara Adhunik Medical College, Dhaka, 2Associate Professor, Department of F.Med,
Monno Medical College, Dhaka
ABSTRACT
Introduction: Viral hepatitis, either acute or chronic, may lead to nephropathies as one of its multiple extrahepatic complications
which often remain clinically silent for a long period and are overlooked. Proteinuria can be a useful tool for early detection of the
underlying renal impairment. This study was undertaken to detect the presence of proteinuria and to assess and compare the level
of proteinuria in HAV and HEV- infected cases; the two most common causes of acute hepatitis in Bangladesh. Method: For this
100 diagnosed patients of HAV & HEV (50 each) hepatitis were screened for isolated proteinuria in a random spot urine sample
during their 3rd to 4th post-ecteric follow ups. Result: 43% HAV and 45% HEV patients had high spot urinary protein with maximum
incidence (54 %) occurring in 3rd decades of life. The pattern of isolated proteinuria was significantly different in HAV vs HEV cases.
The mean ± SD value of spot urinary protein of HEV females was significantly higher than that of HAV where highest rate (64%) of mild
proteinuria was observed in HAV and maximum number (46%) of moderate proteinuria in HEV patients. Conclusion: Spot urinary
protein concentration should be checked quantitatively in every HEV as well as HAV- hepatitis patient even when clinically improved.
Keywords: Isolated proteinuria, Nephropathy, Viral hepatitis
a wide range of extrahepatic features, including renal
disease. But, extra-hepatic manifestations are unusual
in hepatitis A, and renal manifestations are even more
infrequent. Still, a variety of renal manifestations
can be observed in patients with HAV infection who
are biochemically stable (normal aminotransferase
levels).2,7,8 Such patients may present with proteinuria
in their post-icteric phase which can be detected
during their third or fourth follow-up. Hepatitis
itself can cause proteinuria which usually subsides
within the first week of jaundice.6,7 Thus, patients
with both HAV or HEV infections are recommended
to be followed up 3-4 weeks after discharge, and if
necessary at monthly intervals for next 3 months5 as
relapse may occur even after complete recovery9 or
course may be prolonged (abnormal aminotransferase
levels) even more than 14 weeks10 resulting in a
complicated outcome with atypical manifestations.
The abscense of severe liver disease precludes a
missed diagnosis of underlying renal manifestations.2,6
Proteinuria, a simple test in practice, can be a useful
tool for early detection of the underlying renal
impairment to halt further disease progression and
for effective interventions. This study was undertaken
to evaluate and compare the prevalence as well as
the degree of proteinuria in HAV and HEV- hepatitis
patients.
INTRODUCTION
Hepatitis A and E virus (HAV & HEV) are the most common
causes of acute hepatitis and are endemic in South Asia;
specially in the developing countries, like the Indian
subcontinent1,2 as well as in Bangladesh.2,3 Both viruses
generally cause an acute, self-limiting illness followed by
a complete recovery. Recent studies have shown that both
HAV and HEV can result in severe disease and a poor
outcome. The overall estimated mortality rate associated
with hepatitis A is 0.1% to 0.3%, but this rises to 1.8% over
the age of 50.2,4 On the other hand, HEV draws most of the
attention due to the poorly understood case fatality rate
(>20%) in infected pregnant women, especially in their
second and third trimesters.5
Though complete recovery without squeal is the usual
outcome in these two enteric viral hepatitis, relapsing
form can be seen in 3-20% of the case. Clinically
demonstrable renal disease accounts for about 44.8%
of all extrahepatic manifestations secondary to viral
hepatitis and can occur in acute or chronic cases, which
either may precede or follow overt liver disease6. The
exact mechanism(s) involved are not known yet but
immune complex formation may be an important
etiological factor.2,7 HEV infection is associated with
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2. Nargis and Ahamed: Proteinuria in viral hepatitis
METHODS
A total of 100 diagnosed cases of HAV & HEV (50 each)
hepatitis were selected purposively during their 3rd to
4th follow up in post-ecteric phase. The primary selection
was based on the history, physical examination and
laboratory findings with positive anti-HAV or anti-HEV
antibody, normal serum total bilirubin & serum alanine
transaminase (ALT). The non smoker, non alcoholic
subjects who willingly participated in the study were
duly instructed for sample collection. The random spot
urine specimens were collected along with 5 ml of blood
to conduct all the relevant tests. The specimens were
stored appropriately until analyzed. The cases with
raised fasting plasma glucose (for diabetes), total bilirubin
(acute hepatitis), ALT (for acute state of illness), TG, total
cholesterol (for dyslipidaemia, AGN, nephritic syndrome),
serum creatinine and decreased Ccr (for pre-existing
renal impairment), with raised BP (for hypertension)
and in pregnancy were excluded. The study subjects
were selected from the Department of Hepatology,
and the biochemical tests were done at the Department
of Biochemistry, Bangabandhu Sheikh Mujib Medical
University (BSMMU). The spot urinary protein was
measured by Pyrogallol red molybdate method.9 The spot
urinary protein <10 mg/dl was defined as trace or normal,
≥10 mg/dl as mild proteinuria, >30 mg/dl as moderate and
>100 mg/dl as heavy proteinuria.10 All the collected raw
data was organized and analyzed into statistical format
by using SPSS 12.0 for windows software.
RESULTS
Of all the cases of post viral hepatitis variable amount of spot
urinary protein was detected in a total of 88 cases (43 HAV
and 45 HEV cases). The age range of the selected subjects
was 12 to 35 years with maximum incidence (54 %) occurring
in 3rd decades of life. Distribution of study subjects according
to age, sex is shown in Figure 1. The spot urinary protein
in HAV and HEV study subjects were compared according
to three age ranges (<20, ≥20 and ≥30 years), sex and the
degree of proteinuria, respectively. The mean ± SD value of
spot urinary protein of HEV was higher than that of HAV
though statistically not significant (27.08 ± 14.9 mg/dl vs
22.54 ± 8.7 mg/dl; p>0.05). However, significant difference
was revealed at 3rd decade of life (>20 years) when mean
spot urinary protein of HAV and HEV was compared
among different age ranges (Table-I) and in females when
compared by sex (Table-II).
Out of the total 100 subjects majority (54 %) of cases had mild
proteinuria. Among the rest, 34% had moderate and 12%
had trace proteinuria. The frequency distribution of degree
of spot urinary protein showed significant difference
between HAV and HEV study subjects (Table-III). Majority
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Table 1: Comparison of spot urinary protein in different
age groups of HAV and HEV cases
Age groups
(years)
Spot urinary protein [mean±SD (mg/dl)] p‑value*
<20 27.76±7.8 34.60±20.3 >0.05
≥20 20.76±7.7 26.71±13.6 <0.05
≥30 13.25±8.1 20.00±8.7 >0.05
*Unpaired ‘t’ test
Table 2: Comparison of spot urinary protein in different
age groups of HAV and HEV cases
Sex Spot urinary protein [mean±SD (mg/dl)] p‑value*
HAV HEV
Male 22.19±9.2 24.29±14.1 >0.05
Female 22.96±8.3 30.64±15.5 <0.05
*Unpaired ‘t’ test
Table 3: Comparison of degree of spot urinary protein of
male and female between HAV and HEV cases
Proteinurian (mg/dl) HAV (%) HEV (%) p‑value*
Trace (≤10) 7 (14) 5 (10) <0.05
Mild (11‑30) 32 (64) 22 (44)
Moderate (31‑100) 11 (22) 23 (46)
*Unpaired ‘t’ test
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HAV HEV
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Figure 1: Distribution of study subjects according to age range and sex
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3. Nargis and Ahamed: Proteinuria in viral hepatitis
cases) of enteric viral hepatitis. Such higher prevalence
could be explained by the endemicity and the variable
seroprevalence with different genotypes of both HAV and
HEV in South Asian populations. The epidemiology of
HEV is complex, and unlike other enteric pathogens such
as hepatitis A virus (HAV), HEV infection is more common
in the second and third decades of life in endemic South
Asian populations, whereas infection with HAV is more
frequent in young children.16,17 This again may relate to
the higher rate (54%) of proteinuria in the study subjects
at their 3rd decade of life. The age-specific prevalence
estimates seen in this study reflect an unusual distribution
with 52% peak of higher degree (moderate) of proteinuria
at early (2nd) decade of life and highest incidence of mild
proteinuria at 3rd (62%) and 4th (54%) decade of life. Here,
prevalence of mild proteinuria was higher in younger HAV
patients (HAV vs HEV was 42% vs 32% and 4% vs 10%
in 3rd and 4th decades of life respectively). The mean spot
urinary protein in early age group (2nd decade) was higher
than the middle age group (3rd and 4th decades) of both
HAV and HEV study subjects with greater values in HEV
cases.18,19 This may be contributed by the unequal number
of patients in different age groups and the smaller sample
size of our study.
Epidemiological studies have shown that in some individuals
[particularly children] leads to the development of nephritic
syndrome with strong male predominance. But, the highest
mean in this study is observed in female HEV cases (30.64 ±
15.5 mg/dl); though degree of proteinuria was close in
HAV and HEV cases when compared by sex. Sherilock, S,
2002 explained the fact as the marked differences in the
epidemiology of HAV infection between continents and
regions.16 It can be assumed that prevalence as well as the
degree of proteinuria in different age groups and sex of
HAV and HEV patients is significantly different which
may coincide with the impending renal involvement in
these patients.
of the cases (52%) at 2nd decade of life showed moderate
proteinuria whereas highest incidence of mild proteinuria
was observed in 3rd (62%) and 4th (54%) decade of life with
HAV vs HEV of 42% vs 32% and 4% vs 10% cases respectively
(Figure 2a 2b).
DISCUSSION
Total urinary protein excretion in the normal adult should
be less than 150 mg/day. Higher rates of protein excretion
that persist beyond a single measurement should be
evaluated, as they often imply an increased glomerular
permeability.11 Isolated proteinuria is defined as proteinuria
without hematuria or a reduction in glomerular filtration
rate (GFR). In most cases of isolated proteinuria, the
patient is asymptomatic, and the presence of proteinuria is
discovered incidentally by use of a dipstick during routine
urinalysis. The urine sediment is unremarkable (fewer
than three erythrocytes per high power field and no casts),
protein excretion is less than 3 g/day (non-nephrotic),
serologic markers of systemic disease are absent, and there
is no edema, hypertension, diabetes, or hypoalbuminemia.12
Proteinuria, in people with a normal GFR, is associated
with an increase in adverse clinical outcomes, even when
excretion of protein is as low as 7 mg/day.11 The method
most commonly used to measure urinary protein relies on
24-hour urine collection, which is the gold standard but is
time consuming, cumbersome, and often inaccurate and
imprecise. An alternative approach avoiding timed urine
collections is the measurement of the protein: Creatinine
ratio in single random urine specimens.13 But the ratio is
influenced by urinary creatinine excretion, which can vary
considerably among individuals.14 Hence a spot urine
examination for protein would be more acceptable and less
time consuming.9,15
In this study significant amount of spot urinary protein
was detected in 88% cases (43% HAV and 45% HEV
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(a) (b)
Figure 2: Comparison of degree of spot urinary protein in HAV vs HEV cases by a) different age groups and b) sex
87 Acta Medica International | Jul - Dec 2014 | Vol 1 | Issue 2 |

4. Nargis and Ahamed: Proteinuria in viral hepatitis
CONCLUSION
The observations presented in this study indicates that
prevalence as well as the degree of proteinuria in different
age groups and sex of HAV and HEV patients is significantly
different which may coincide with the impending renal
involvement in these patients. Thus, spot urinary protein
concentration should be checked in every HAV and
HEV hepatitis patient to detect the presence and level of
proteinuria. Vaccination should be encouraged in high risk
groups. Patients should be monitored for proteinuria even
after recovery for early detection and intervention. Further
prospective study of spot urinary protein estimation with
larger sample size should be done to evaluate the extent of
renal impairment in such patients.
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How to cite this article: Nargis W, Ahamed BU. Isolated proteinuria in
hepatitis A versus E virus (HAV vs HEV) infected patients: A hospital based
observational study. Acta Medica International 2014;1(2):85-88.
Source of Support: Nil, Conflict of Interest: None declared.
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