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Brazilian Journal of Microbiology (2024) 55:357–364
https://doi.org/10.1007/s42770-023-01197-7
CLINICAL MICROBIOLOGY - RESEARCH PAPER
Seroprevalence ofhepatitis E virus inpatients withchronic liver
disease
LílianRoseMaiaGomesdeAraújo1,2 · AndreaDóriaBatista2· MariaRosângelaCunhaDuarteCôelho3·
JoelmaCarvalhoSantos4· GabrielGalindoCunha3· GabrielaRodriguesAguiarLeal1,3· JoãoRenatoRebelloPinho5·
AnaLúciaCoutinhoDomingues1,2· EdmundoPessoaLopes1,2,6
Received: 8 August 2023 / Accepted: 22 November 2023 / Published online: 21 December 2023
© The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia 2023
Abstract
Introduction The seroprevalence of hepatitis E virus (HEV) in patients with chronic liver disease (CLD) is little known in
Brazil. Studies have suggested that HEV may harmfully influence the course of CLD, with a higher risk of progression to
cirrhosis.
Objective To estimate the prevalence of the anti-HEV antibody (IgG) in patients with CLD and to describe demographic
data and risk factors, as well as clinical-laboratory and ultrasound parameters.
Patients and methods Cross-sectional study that included 227 patients with CLD followed at a referral outpatient clinic
from June 2022 to March 2023. The patients were investigated clinically and tested for liver functions, anti-HEV IgG and,
in positive cases, for HEV-RNA. Ultrasonography of the upper abdomen was also carried out.
Results Investigation of 227 patients (50 with hepatitis B, 49 with nonalcoholic fatty liver disease, 33 with hepatitis C, 17
with alcoholic liver disease, 16 with schistosomiasis and 62 with mixed disease), 55.5% were female, with an average age
of 57 ± 13years; 37.9% had liver cirrhosis. Seven patients (3.08%) presented anti-HEV positive and HEV-RNA negative.
Ultrasound identified association between anti-HEV and contact with pigs, presence of gynecomastia or palmar erythema,
lower platelet count, higher APRI and FIB-4 values, and splenomegaly.
Conclusion Although the prevalence of anti-HEV in patients with CLD was low in this study, the antibody was observed more
frequently in cases with a history of contact with pigs and with clinical-laboratory or imaging evidence of more advanced
chronic liver disease.
Keywords Hepatitis E virus· Hepatitis E· Seroprevalence· Liver cirrhosis
Responsible Editor: Beatriz Ernestina Cabilio Guth
* Lílian Rose Maia Gomes de Araújo
maia_lilian@hotmail.com
* Edmundo Pessoa Lopes
epalopes@uol.com.br
1 Postgraduate Program inTropical Medicine, Center
ofMedical Sciences, Universidade Federal de Pernambuco
(UFPE), Recife, Brazil
2 Gastroenterology Division, Hospital das Clínicas –
Universidade Federal de Pernambuco (UFPE), Avenida
Professor Moraes Rego, 135, Recife, Pernambuco50670-901,
Brazil
3 Laboratory ofVirology, Keizo Asami Institute (LIKA),
Departament ofPhisiology andPharmacology, Universidade
Federal de Pernambuco (UFPE), Recife, Brazil
4 Laboratory ofImmunohematology, Hemocentro de Alagoas
(Hemoal), Maceió, Brazil
5 Laboratory ofGastroenterology andTropical Hepatology,
Institute ofTropical Medicine andDepartment
ofGastroenterology, Faculty ofMedicine, Universidade de
São Paulo, SãoPaulo, SP, Brazil
6 Department ofInternal Medicine, Center ofMedical
Sciences, Universidade Federal de Pernambuco (UFPE),
Recife, Brazil
358 Brazilian Journal of Microbiology (2024) 55:357–364
1 3
Introduction
The hepatitis E virus (HEV), a positive-sense, single-
stranded RNA virus, is classified in the Hepeviridae fam-
ily, genus Orthohepevirus, species A, with eight geno-
types currently recognized (HEV-1 to HEV-8). Genotypes
HEV-1 to HEV-4 have been detected in humans, while
HEV-5 and HEV-6 are genotypes strictly found in wild
boars; and genotypes HEV-7 and HEV-8 are found in cam-
els and dromedaries [1]. Two of these genotypes (HEV-1
and HEV-2) only infect humans. The HEV-3 and HEV-4
genotypes are endemic in animal species such as pigs and
wild boars; These strains cause zoonotic infections in
humans, through the consumption of contaminated meat
or direct contact [2].
Contagion by the HEV-1 and HEV-2 genotypes occurs
through the oral-fecal route, by consumption of contami-
nated water, causing diseases in areas with fragile sanitary
infrastructure, as occurs in India. Sporadic cases are com-
mon, but can be responsible for large outbreaks, involving
hundreds or thousands of cases [3].
The HEV-3 and HEV-4 genotypes infect humans spo-
radically as accidental hosts, through the consumption of
contaminated pork products, causing normally asympto-
matic infections in immunocompetent patients. These gen-
otypes may progress to chronic hepatitis and cirrhosis of
the liver in immunocompromised patients, such as trans-
plant recipients and people living with HIV. Occasionally,
infection may be associated with extrahepatic manifesta-
tions: neurological and hematological [4].
In recent years, HEV has drawn attention with increased
reporting of autochthonous cases of hepatitis from indus-
trialized countries. Hepatitis E had been considered a rare
disease in these countries and observed only in travelers
returning from endemic areas in Africa and Asia. The
autochthonous cases described in industrialized countries
were caused by the HEV-3 and HEV-4 genotypes, with
epidemiological and clinical characteristics distinct from
the HEV-1 and HEV-2 genotypes, which were already cir-
culating in developing countries [5].
HEV is the leading cause of acute enterically transmit-
ted hepatitis worldwide [6]. According to the latest WHO
report, HEV is responsible for about 20 million infections
per year, with more than 3 million symptomatic infections
and 44,000 deaths worldwide in 2015 [7]. In a meta-anal-
ysis carried out to evaluate the global prevalence of HEV,
involving 287 studies and 1,099,717 patients, a percentage
of anti-HEV IgG of 12.47% was found. Data were strati-
fied to estimate the prevalence of anti-HEV in 75 countries
across six continents. The highest rate of anti-HEV IgG
seropositivity was found in Africa (21.76%), followed by
Asia (15.80%), Europe (9.31%), North America (8.05%),
South America (7.28%) and Oceania (5.99%). Data were
also collected in relation to genotyping, with the finding
that genotype 1 infection occurred commonly in India and
occasionally in China, and that genotype 3 was widely
distributed in European countries [8].
In Brazil, a systematic review published in 2019 identified
a global seroprevalence of HEV of 6% (95% CI: 5.0–7.0),
but with great heterogeneity between studies (86.7%), rang-
ing from 0% (95% CI: 0.0–3.0) to 10% (95% CI: 7.0–15.0).
In the subgroup analysis, the prevalence of anti-HEV was
7% in blood donors and 3% in the general population [9],
suggesting that HEV infection in Brazil is not rare.
Chronic infection with HEV genotype 3 is found in immu-
nocompromised patients in European countries. In solid
organ transplant recipients, HEV RNA positive active infec-
tion, has been detected in 1 to 2% of cases [10]. Although the
exact amount of chronicity is different between the various
studies, it is assumed that HEV infections become chronic
in about two-thirds of solid organ recipient patients [11].
Little is known about the prevalence of HEV in patients
with chronic liver disease (CLD). A study of anti-HEV IgG
seroprevalence conducted in California, USA, found a rate
of 6.6% in patients with alcohol-associated CLD, 8.7% in
patients with hepatitis C, 8.8% in patients with nonalcoholic
fatty liver disease (NAFLD) and 19.9% in patients with hep-
atitis B [12]. Another study, conducted in Vienna, Austria,
found a prevalence of 26.3% of anti-HEV IgG in patients
with NAFLD, with seropositivity being independently
associated with a higher risk of cirrhosis [13]. Although
restricted to a single etiology for liver cirrhosis, the study
suggests that the association of HEV with CLD may nega-
tively influence the progression of the disease to cirrhosis.
Due to the possibility of worsening of CLD by the hepati-
tis E virus, this study aimed to verify the prevalence of anti-
HEV IgG and its association with demographic data, risk
factors, clinical-laboratory and ultrasonographic exams in
patients with CLD of different etiologies followed in a Hepa-
tology outpatient clinic of a reference hospital in Recife-PE.
Material andmethods
Study design
This is a cross-sectional study, developed at the Hepatology
Outpatient Clinic of the Hospital das Clínicas of the Federal
University of Pernambuco (HC-UFPE).
Patients
The minimum sample size for the development of the study
was 134 patients. The sample size calculation was performed
using the EPI-INFO program version 7.2.2.16, establishing
359Brazilian Journal of Microbiology (2024) 55:357–364
1 3
an error of 5%, reliability of 95% and expected proportion of
anti-HEV IgG of 8.61% in patients with CLD [12].
We included patients older than 18years, with a diagno-
sis of CLD of the following etiologies: NAFLD, alcoholic,
hepatitis B, hepatitis C, schistosomiasis and mixed disease
(more than one etiology) who were seen between June 2022
and March 2023. Schistosomiasis was diagnosed by personal
history and presence of periportal fibrosis identified by ultra-
sound. Patients diagnosed with acute liver diseases, liver or
kidney transplants, people living with HIV/AIDS or using
immunosuppressants were excluded.
Method
After signing the Free and Informed Consent Form, the
patients were submitted to an interview to collect sociode-
mographic data and risk factors. Subsequently, a physical
examination was performed to evaluate stigmas or signs
of chronic liver disease, portal hypertension or cirrhosis
decompensation. Then, 5mL of blood was collected from a
peripheral vein for use in anti-HEV research. ELISA com-
mercial kits (EUROIMMUN®, Germany) were used, and
examined at the Virology Laboratory of Keizo Asami Insti-
tute (LIKA-UFPE). In patients with positive anti-HEV IgG,
HEV RNA was tested by real-time PCR using the RealStar
kit (HEV RT-PCR kit 2.0, Altona Diagnostics®, Germany),
in the Virology Laboratory of Albert Einstein Diagnostic
Medicine.
The following complementary tests were performed
within 3months of blood collection. The serum activities
of aminotransferases (ALT and AST), bilirubin, Gamma-GT,
Albumin, platelet count and INR (International Normal-
ized Ratio). These were analyzed in the central laboratory
of HC-UFPE. Ultrasonography of the upper abdomen was
performed at HC-UFPE by two experienced examiners.
The study was approved by the Ethics and Research
Committee of HC-UFPE, number: 5.324.465 and Cer-
tificate of Presentation of Ethical Appreciation number:
55401222.0.0000.8807.
Statistical analysis
Clinical and laboratory data were transcribed in spread-
sheet form and analyzed using IBM SPSS® 26 Statistics,
for Windows, and MedCalc® 20.104 statistical software.
Quantitative variables were described as mean and stand-
ard deviations or median and 25th and 75th percentiles,
depending on the result of the Shapiro–Wilk normality test.
Qualitative variables were described as absolute and relative
frequencies.
Patients were divided into two groups (positive and nega-
tive anti-HEV IgG). Chi-square test and Fisher's exact test
were used to compare categorical variables. The comparison
of means between two independent groups with normal
distribution was based on the unpaired t-test, whereas the
comparison of medians between non-parametric variables
was made through Mann–Whitney test. Association between
exposure (potential risk factors) and outcomes (positive or
negative anti-HEV IgG) was analyzed using prevalence ratio
(PR) at a 95% confidence interval (95% CI). This coefficient
is used as an estimate of odds ratio in cross-sectional stud-
ies with low-frequency outcomes to estimate the chances of
these results in exposed and unexposed subjects [14]. Results
with p < 0.05 were considered statistically significant.
Results
A total of 227 patients met the inclusion criteria, of
which 126 (55.5%) were female, with an average age of
57 ± 13years. The other demographic characteristics are
shown in Table1.
Anti-HEV IgG testing was positive in 7 of the 227
(3.08%) patients with CLD; HEV-RNA testing was negative
in all patients. The risk factors of the 227 patients according
to the serology for anti-HEV are shown in Table1. Only
contact with pigs showed an association with the presence
of anti-HEV-IgG (p = 0.013). Thus, it can be inferred that
patients who had contact with pigs ran a risk at least 7.24
times greater of having anti-HEV IgG, when compared to
those who had no contact with pigs, and that this increase
was statistically significant (p = 0.016).
The clinical characteristics of the 227 patients with CLD
are described in Table2. An association was observed
between anti-HEV-IgG and the presence of gynecomastia
(p = 0.041) and palmar erythema (p = 0.07). Thus, it can
be inferred that patients with gynecomastia and erythema
presented a risk at least 7.62 and 4.27 times greater, respec-
tively, of having anti-HEV, when compared to those who did
not have gynecomastia or erythema, and that this increase
was significant (p = 0.009 and p = 0.049, respectively).
According to the etiology of CLD, patients had the fol-
lowing distribution: 50 with hepatitis B, 49 with NAFLD,
33 with hepatitis C, 17 with alcoholic liver disease, 16 with
schistosomiasis and 62 with mixed disease (more than one
etiology). Eighty-six (37.9%) of them already had liver cir-
rhosis (Table3). Anti-HEV IgG was not more frequent in
patients with cirrhosis (p = 0.114).
The 7 patients with positive anti-HEV IgG had the fol-
lowing etiologies of CLD: 2 with alcoholic liver disease,
1 with hepatitis C, 1 with schistosomiasis, 1 with hepatitis
C and schistosomiasis, 1 with alcoholic liver disease and
schistosomiasis and 1 with hepatitis B and schistosomiasis.
Four of the 7 patients with positive anti-HEV (p = 0.021) had
schistosomiasis as the etiology of CLD (Table3).
360 Brazilian Journal of Microbiology (2024) 55:357–364
1 3
In the laboratory (Table4) and imaging (Table5) evalu-
ations, an association was observed between anti-HEV-IgG
and lower platelet counts (p = 0.006), higher APRI values
(p = 0.011) and FIB 4 (p = 0.007). On ultrasonography, an
association was observed between anti-HEV and spleno-
megaly (p = 0.04).
Discussion
In recent years, there has been a growing interest in HEV
infection and its repercussions, such as the possible associa-
tion with more severe liver diseases. Given this, our study
was developed to evaluate the occurrence of anti-HEV
in patients with CLD from a reference center in Recife,
Pernambuco.
We found 7 cases (3.08%) with positive anti-HEV among
the 227 patients with CLD and all presented negative HEV-
RNA research.
Serological surveys on HEV carried out in Brazil, in
blood donors, have revealed the following results. In Per-
nambuco the prevalence of anti-HEV IgG was found to be
0.9% [15], in Mato Grosso 4% [16], in São Paulo 9.8% [17],
while in Rio Grande do Sul prevalence of 40.25% [18] and
in Santa Catarina 10% [19]. The highest seroprevalence,
detected in the South of Brazil, is explained because it is
the region with the highest activity in pig farming and the
highest consumption of pork and pork products.
Due to the chronification of HEV in immunosuppressed
people, the number of investigations of these patients has
increased. In people living with HIV, seroprevalence of anti-
HEV IgG has been found to be 4.1% in Pernambuco [20], in
Rio Grande do Sul 6.7% [21] and in São Paulo 10.7% [22].
Table 1 Demographic
characteristics and risk factors
of 227 patients with chronic
liver disease, according to anti-
HEV IgG serology,Recife, 2023
a Fisher's Exact Test; b,unpaired t-Test; c Chi-Square test; dZ test
* Expressed as mean ± SD
95% CI 95% confidence interval; PR Prevalence ratio
Variables Anti-HEV IgG pRP 95% CI pdTotal
Positive Negative
n%n%n%
Sexo
Male 4 57.10% 97 44.10% 0.703a1.66 0.38–7.26 0.499 101 44.50%
Female 3 42.90% 123 55.90% 126 55.50%
Idade* 57 ± 11 57 ± 13 0.962b − − − 57 ± 13
Etnia
Black 1 14.30% 15 6.80% 0.556c− − − 191 84.10%
Mixed 6 85.70% 185 84.10% 1.99 0.25–15.5 0.512 16 7.00%
White 0 0.00% 20 9.10% 3.71 0.16–85.3 0.413 20 8.80%
Native 0 0.00% 0 0.00% 0.17 0.01–2.12 0.171 0 0.00%
Treated water
Yes 7 100.00% 196 89.10% 1.000a1.84 0.11–31.2 0.674 203 89.40%
No 0 0.00% 24 10.90% 24 10.60%
Sanitation
Yes 6 85.70% 166 75.50% 1.000a1.92 0.24–15.6 0.542 172 75.80%
No 1 14.30% 54 24.50% 55 24.20%
Education
Illiterate 0 0.00% 16 7.30% 0.204c − − − 16 7.10%
Elementary school 3 42.90% 124 56.60% 1.07 0.06–19.9 0.961 127 56.20%
High school 2 28.60% 63 28.80% 0.78 0.04–15.5 0.868 65 28.80%
Higher education 2 28.60% 16 7.30% 0.22 0.01–4.3 0.322 18 8.00%
Contact with pigs
Yes 5 71.40% 53 24.20% 0.013a7.24 1.44–36.3 0.016 58 25.70%
No 2 28.60% 166 75.80% 168 74.30%
Consumption of pigs
Yes 4 57.10% 121 55.30% 1.000a1.07 0.25–4.7 0.921 125 55.31%
No 3 42.90% 98 44.70% 101 44.69%
361Brazilian Journal of Microbiology (2024) 55:357–364
1 3
Among renal transplant recipients, the seroprevalence
of anti-HEV IgG was found to be 2.5% in Goiás [23] and
3.1% [24] and 15% [25] in two medical centers in São
Paulo. In these two studies from São Paulo, HEV-RNA
was found, respectively, in 3.1% [24] and 10% [25] of the
transplant recipients. among liver transplant recipients, the
seroprevalence of anti-HEV IgG was 8.1% in São Paulo
[26].
Table 2 Clinical characteristics
of 227 patients with chronic
liver disease, according to
anti-HEV IgG serology, Recife,
2023
a Fisher's Exact test; bZ test
95% CI 95% confidence interval; PR Prevalence ratio
Variables Anti-HEV IgG paRP CI 95% pbTotal
Positive Negative
n%n%n%
Jaundice
Yes 1 14.30% 31 14.10% 1.000 1.02 0.13–8.16 0.988 32 14.10%
No 6 85.70% 189 85.90% 195 85.90%
Ascites
Yes 0 0.00% 15 6.80% 1.000 0.89 0.05–14.8 0.933 15 6.60%
No 7 100.00% 205 93.20% 212 93.40%
Erythema
Yes 3 42.90% 30 14.00% 0.070 4.27 1.0–18.2 0.049 33 14.90%
No 4 57.10% 184 86.00% 188 85.10%
Spider
Yes 2 28.60% 20 9.30% 0.146 3.82 0.79–18.5 0.096 22 10.00%
No 5 71.40% 194 90.70% 199 90.00%
Gynecomastia
Yes 2 28.60% 9 4.20% 0.041 7.63 1.66–35.0 0.009 11 5.00%
No 5 71.40% 205 95.80% 210 95.00%
Hair rarefaction
Yes 1 14.30% 14 6.50% 0.393 2.29 0.29–17.8 0.429 15 6.80%
No 6 85.70% 200 93.50% 206 93.20%
Cirrhosis
Yes 5 71.40% 81 36.80% 0.108 4.09 0.81–20.7 0.087 86 37.9%
No 2 28.60% 139 63.20% 141 62.1%
Table 3 Distribution of the
etiological of chronic liver
disease in the 227 patients,
according to anti-HEV IgG
serology, Recife, 2023
* The Chi-Square test. NAFLD Nonalcoholic fatty liver disease
Etiology of the chronic liver disease Anti-HEV-IgG p * Total
Positive Negative
n%n%n%
Hepatitis B 0 0,00% 50 22,70% 0,126 50 22,00%
DHGM 0 0,00% 49 22,30% 49 21,60%
Hepatitis C 1 14,30% 32 14,50% 33 14,50%
Alcohol, 2 28,60% 15 6,80% 17 7,50%
Schistosomiasis 1 14,30% 15 6,80% 16 7,00%
Chronic liver disease mixed 3 42,90% 59 26,80% 62 27,30%
Alcohol + Schistosomiasis 1 33.33% 7 11,86% 8 12,90%
Hepatitis B + Schistosomiasis 1 33.33% 2 3,39% 3 4,84%
Hepatitis C + Schistosomiasis 1 33.33% 5 8.47% 6 9,68%
-NAFLD + schistosomiasis 0 0,00% 4 6,78% 4 6,45%
-Other 0 0,00% 41 69,49% 41 66,13%
362 Brazilian Journal of Microbiology (2024) 55:357–364
1 3
Table 4 Laboratory
characteristics of 227 patients
with chronic liver disease,
according to anti-HEV IgG
serology, Recife, 2023
a unpaired t-Test; bMann-Whitney u test. c−Chi-Square test
* Expressed as mean ± SD; **Values at the median (P25-P75). ALB Albumin; ALT Alanine aminotransferase;
APRI The index of the relationship of normal for the institution on the platelet count; AST Aspartate ami-
notransferase; FA Alkaline phosphatase; FIB-4 Index and fibrosis-4; GGT Gamma-glutamyl transferase;
INR International normalized ratio; MELD Model for liver disease end-stage
Variable Anti-HEV-IgG pTotal
Positive Negative
n, % n, % n, %
Platelet count (/mm3)* 99.571 ± 91.659 180.971 ± 75.273 0.006a178.283 ± 77.004
INR* 1,31 ± 0,26 1,16 ± 0,25 0,126a1,17 ± 0,26
ALT (IU/L)* 33 (26–44) 33 (23–49) 0,900b33 (23–47)
AST (IU/L)* 43 (29–46) 31 (24–47) 0,280b31 (24–46)
BT (mg/dL)** 0.96 (0,87- 1.6) 0.7 (0,46–1,1) 0,061b0.72 (0.46- 1.13)
FA (IU/L) * 101 (71–118) 77 (58–96) 0,308b77 (58–97)
GGT (IU/L)* 88 (61–165) 49 (29–110) 0,111b50 (29–116)
ALB (g/dL)** 4 (3,4–4,5) 4,3 (3,9–4,5) 0,322b4.3 (3.9—4.5)
APRI** 1.47 (0.55 -1.69) 0,45 (0,27–0,85) 0,011b0,46 (0,27–0,87)
FIB-4** 6,00 (2,69–9,15) 1,76 (1,02–3,66) 0,007b1,78 (1,03–3,77)
Child–Pugh classification
A 4 80.00% 53 75,70% 0,893c, 57 76.00%
B 1 20,00% 14 20,00% 15 20,00%
C 0 0,00% 3 4,30% 3 4,00%
MELD
≤ 9 2 40,00% 34 48,60% 0,755c36 48,00%
10 -19 3 60,00% 32 45,70% 35 46,70%
≥ 20 0 0,00% 4 5,70% 4 5,30%
Table 5 Imaging characteristics
of patients with chronic liver
disease, according to anti-HEV
IgG serology, Recife, 2023
a Chi-Square Test; b−Test, Mann–Whitney u test; c,Fisher's Exact Test;
* The values in the median (P25-P75). US Ultrasonography
Variables Anti-HEV IgG pTotal
Positive Negative
n%n%n%
US, irregularity of the surface
Missing 2 28,60% 92 52,30% 0,310a94 51,40%
Lighter 1 14,30% 26 14,80% 27 14,80%
Crude 0 0,00% 12 6,80% 12 6,60%
Lobulada 4 57,10% 46 26,10% 50 27.3%
US, texture,
Homogeneous 2 28,60% 88 50,00% 0,444a90 49,20%
Heterogeneous 5 71,40% 88 50,00% 93 50,80%
Spleen (cm)* 13.4 (12.0 a-17,7) 12,0 (9.7–12.0 a) 0,044b12.0 9.7–12.2)
Portal vein (cm.) * 1,2 (0,90–1,60) 1,1 (0,96–1,20) 0,372b1,1 (0,96–1,20)
Side - Yes 2 28,60% 14 8,00% 0,119c16 8,80%
No 5 71,40% 160 92,00% 165 91,20%
Ascites Sim 1 14,30% 14 8,00% 0,460c15 8,30%
No 6 85,70% 160 92,00% 166 91,70%
363Brazilian Journal of Microbiology (2024) 55:357–364
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A retrospective multicenter study, with data from 17
centers in Europe and the United States, evaluated 85
HEV-infected solid organ transplant recipients. Of these,
56 patients (65.9%) developed chronic hepatitis, 8 patients
(9.4%) developed liver cirrhosis and 2 died from complica-
tions of cirrhosis [27].
A study conducted in Bahia revealed a prevalence of
12.95% of anti-HEV IgG in 301 patients with CLD. The etiolo-
gies included were hepatitis B, hepatitis C, autoimmune hepa-
titis, and drug-induced liver injury (DILI). When stratified by
groups, drug-induced liver injury had the highest prevalence
(21.1%) of anti-HEV [28]. It is possible that the differences in
the tested population may have been responsible for the higher
prevalence of anti-HEV in Bahia, in relation to the prevalence
found in our study. In addition, the distribution of the etiologies
of CLD was different in the two states, since in Bahia patients
with autoimmune hepatitis and DILI were included, being the
most frequent anti-HEV in those with DILI.
In the present study, gender and age were not associated
with the presence of anti-HEV IgG. However, some authors
have suggested that advanced age and male gender may be
associated with anti-HEV seroprevalence, possibly due to
greater exposure throughout life [12].
Regarding risk factors, in this study there was an associa-
tion between anti-HEV IgG and contact with pig farming,
but no association was observed related to the ingestion of
pork meat. A study in Pernambuco revealed positivity of
anti-HEV IgG in 81.25% of the 96 pigs sent to slaughter-
houses [29]. This confirms the frequent occurrence of HEV
in our country. There did not seem to be any association of
anti-HEV IgG with pork intake, possibly due to the fact that
pork is usually well cooked in our environment. In addition,
pork has a high cost and this study involved patients from the
public system, who have lower purchasing power and more
restricted pork consumption.
However, a Brazilian study conducted with 80 patients
with schistosomiasis mansoni, found anti-HEV IgG in 15
cases (18.8%). This high prevalence was attributed to the
involvement of almost 1/3 of schistosomal patients with
advanced patterns of fibrosis and portal hypertension. These
cases are subject to more episodes of digestive bleeding and,
consequently, greater exposure to hospital environments and
endoscopic procedures [30]. In fact, in our study, a higher
occurrence of anti-HEV was also observed in cases with
CLD involving schistosomiasis mansoni in the etiology.
Additionally, other studies have shown a higher preva-
lence of anti-HEV IgG in patients with cirrhosis when
compared to those with less advanced stage CLD. In fact,
Paternostro etal. evaluated 167 patients with NAFLD and
observed 44 (26.3%) patients with positive anti-HEV IgG,
being the most frequent antibody in those with cirrhosis
(18.2 vs 6.5%, p = 0.024) [13]. In another study involving
patients with hepatitis C, a higher prevalence of anti-HEV
IgG was also found in cirrhotic patients (13.2% vs 8%,
OR:1.74, p = 0.04) [31].
In our study, no association of anti-HEV IgG with cir-
rhosis was found. An association was detected, however,
with some variables related to more advanced CLD. For
example, physical examinations of the participants identified
an association of anti-HEV IgG with gynecomastia and a
tendency to association with palmar erythema (p = 0.07). In
addition, patients with gynecomastia or erythema were more
likely to present IgG antibody against HEV. These stigmata
of chronic liver disease are due to hyperestrogenism, which
is common in liver failure.
In the laboratory evaluation, there was an association of
anti-HEV IgG with thrombocytopenia, one of the first labora-
tory manifestations of portal hypertension. Ultrasound exam-
inations also showed a larger size of the spleen in cases with
positive anti-HEV, which could be related to hypersplenism.
Bilirubin serum levels increased in cases with anti-HEV,
at values close to significant (p = 0.061), which also reflects
more advanced CLD. Perhaps, the number of cases with posi-
tive anti-HEV found in this study was insufficient to reveal
greater laboratory evidence of more advanced liver disease;
or, possibly, the number of cirrhotic patients was insufficient
to reveal differences, constituting limitations of this research.
APRI and FIB-4 values were also higher in those patients
with positive anti-HEV IgG. Certainly, these scores indi-
cated more advanced fibrosis in cases where anti-HEV was
induced by thrombocytopenia, since no differences were
observed in serum aminotransferase levels. Additionally,
similar serum levels of aminotransferases between cases
with and without anti-HEV could have been related to the
absence of inflammatory activity caused by HEV, since all
cases with CLD in our study had undetectable HEV-RNA.
The higher occurrence of anti-HEV IgG associated with
these clinical, laboratory and imaging findings, taken together,
suggests that HEV is related to more advanced CLD. How-
ever, by the design of this study, it was not possible to verify
the causal relationship between HEV and more severe CLD.
Conclusion
Although the prevalence of anti-HEV in patients with CLD
was low in this study, the antibody was observed more fre-
quently in cases with a history of contact with pigs and
clinical-laboratory or imaging evidence of more advanced
liver disease.
Declarations
Conflict of interest On behalf of all authors, the corresponding author
states that there is no conflict of interest.
364 Brazilian Journal of Microbiology (2024) 55:357–364
1 3
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