Research Article | Open Access
Ravindra V. Shinde1 , Anjali R. Shinde2, Anjali D. Patil3, S.K. Pawar1, S.T. Mohite1 and S.R. Patil1
1Department of Microbiology, Krishna Institute of Medical Sciences ‘Deemed To Be University” Karad – 415 539, Maharashtra, India.
2Department of Pharmacology, PIMS UrunIslampur – 415 409, Maharashtra, India.
3Department of Ophthalmology, Krishna Institute of Medical Sciences ‘Deemed To Be University” Karad – 415 539, Maharashtra, India.
J Pure Appl Microbiol. 2020;14(3):2047-2051 | Article Number: 6153
https://doi.org/10.22207/JPAM.14.3.45 | © The Author(s). 2020
Received: 09/03/2020 | Accepted: 24/07/2020 | Published: 18/08/2020
Abstract

Acute viral hepatitis(AVH) is caused by Hepatitis A (HAV) and Hepatitis E(HEV). It is major health burden in India. Both the viruses HAV and HEV are primarily transmitted via the faeco-oral course. Study was conducted to determine the seroprevalence of HAV, HEV and rate of co-infection in AVH patients attending rural tertiary care centre. A retrospective laboratory record based study was carried out in rural tertiary health care center located in Western Maharashtra. Laboratory and Medical records of suspected acute viral infection patients were analyzed during study. Study period was June 2014 to July 2018. Commercially available ELISA kits of IgM anti-HAV and IgM anti-HEV were used to analyze serum samples of suspected study participants. Tests were carried out as per the manufacturer’s instructions. A total of 778 acute viral hepatitis cases were included in the study from July 2014 to July 2018 among which 85/778 (10.9 %) detected positive for HAV and 121/778 (15.6%) detected positive for HEV. Co-infection was identified in 6/778(0.8 %). Jaundice, fever fatigue and hepatomegaly were common clinical presentation in HAV, HEV and confection with both viruses in acute viral hepatitis patients. Study indicated low exposure to HAV in childhood bellow 16 years. Co-infection rate was detected high in 16-25 years age group. Vaccination policy against HAV in adolescent age group needed as there is change epidemiological shift of HAV which has been observed in the current study. These data will helps for planning future vaccination strategies, better implementation sanitation program, and safe water supply in this geographic area.

Keywords

Co-infection, hepatitis A virus, hepatitis E virus, seroprevalence

Introduction

Acute viral hepatitis mainly caused by HAV and HEV andis a major problem worldwide1. Communicable diseases are the major health burden in our country.   Viral hepatitis due to primary Hepatitis viruses is endemic in developing and less developed country2. Various studies in different states have been reported cases of viral hepatitis in the country3.Hepatitis A, B, C and E are the four major hepatotropic viruses causing viral hepatitis. HAV and HEV is a non-enveloped RNA virus of the genus Hepetovirus and family Hepeviridae. Both HAV and HEV are primarily spread via the faeco-oral route. Many studies published earlier revelled HAV exposure is common in kids while HEV common among youth. Both the viruses generally cause self-restricting infections. They may confound as fulminant hepatitis which prompts high casualty particularly noted in pregnant females who contracted HEV contamination especially in the second and third trimester. Co-infection with numerous hepatotropic infections has been accounted in different investigation studies carried in intense viral hepatitis with a rate fluctuating from 7-24%.There has been forecast that this co-infection  may build the seriousness of the illness and may have bad prognosis.4 Outbreaks and sporadic instances of hepatitis A and E detailed all around the world  ,however there is firm association  connected with hazardous drinking water, insufficient sanitation, poor cleanliness, lack of  wellbeing administrations and absence of wellbeing training in asset restricted countries.5-7It is difficult to diagnose co-infection clinically and by biochemical analysis, serology and PCR needed to help in timely diagnosis and identification of causative agent .8-9This study will help in anticipation of risk and the management of acute liver failure in youngsters and grown-up. This study was planned to know the magnitude of HAV, HEV and co-infection, its clinical profile in patients with intense (Acute) viral hepatitis in this geographical area.

Materials and Methods

After a study protocol presentation and endorsement from institutional ethics committee(ref. no. KIMSDU/IEC/06/2018), a retrospective laboratory record based study was conducted in rural tertiary health care center located in Western Maharashtra. The document in laboratory and medical records were reviewed and analyzed to retrieve   the Demographic data, Clinical data,and laboratory data. Study period was June 2014 to July 2018. A sum of 778 acute viral hepatitis patients was our study population in a time bound study period.  Serum samples included in study were analyzed for IgM anti-HEV for the detection HEV infection and anti -IgM antibody detection for HAV, using commercially available ELISA kits (Recombilisa CTK Biotch,Inc). Tests were carried out as per the manufacturer’s instructions.

Clinical Criteria
An acute illness with a discrete onset of any sign or symptom consistent with acute viral hepatitis e.g., fever, headache, malaise, anorexia, nausea, vomiting, diarrhea, abdominal pain, or dark urine.

Inclusion criteria
Samples with request of both HAV IgM and HEV IgM were included in this study.

Exclusion criteria
Samples with request of either HAV IgM or HEV IgM were not included in this study. Tests requested for other viral markers such as hepatitis B surface antigen and HCV were also excluded.

Statistical Analysis
The data is summarized into numbers and percentages. Association is tested by applying Chi-Square test. The level of significance was 5%.

RESULTS

Our study revealed overall higher prevalence of HEV(15.6%) than that of HAV (10.9%)in suspected cases of Acute Viral hepatitis. The study also revealed significant association between HEV and HAV in Acute Viral Hepatitis (Chi-Square = 4.541, p = 0.0331). Significantly high proportion of positive HEV were negative for HAV and significantly high proportion of positive HAV were negative for HEV. This resulted in low rate of co-infection, 0.8%, in Acute Viral Hepatitis.

Table (1):
Co-relation between HAV, HEV and Co-infection of both (A&E).

Hepatitis A Hepatitis E Total (%)
Positive (%) Negative (%)
Positive 6 (0.8) 79 (10.1) 85(10.9)
Negative 115 (14.8) 578 (74.3) 693 (89.1)
Total (%) 121(15.6) 657 (84.4) 778

Table (2):
Age specific etiology of acute viral hepatitis.

Age in years
Hepatitis A (%)
n=85
Hepatitis E(%)   n=121
Co-infection(A&E)
n=6
0-4
07  (8.2)
0 (0)
0(0)
5-15
15(17.6)
03(2.4)
0(0)
16-25
38(44.5)
47(38.8)
3(50%)
26- 35
09       (10.5)
49 (40.4)
2(33.3)
36-45
07(8.2)
16(13.2)
1(16.0)
46-55
03(3.5)
03(2.4)
0(0)
>55
06(7)
03(2.4)
0(0)

HAV high seroprevalence was noted in 16-25 years age group (44.5%), HEV seroprevalence was observed in 26-35 years age group (40.4%).Co-infection was high in 16-25 years age group. Lowseroprevalence rate was observed in 0-4 year and above 55years age group

Table (3):
Sex distribution of CO- infection, HAV and HEV in patients presenting acute viral hepatitis.

Sex
Number positive cases n=6   (%)
Hepatitis A (%)
n=85
Hepatitis E(%)   n=121
Male
4(66.6)
46(54.1)
75(61.9)
Female
2(33.3)
39(45.8)
46(38.6)
Total
6
85
121

Male population have higher rate of co-infection rate (66.6%) in comparison with females (33.3%).

Table (4):
Serum alkaline phosphatase in patients with hepatitis.

Serum alkaline phosphatase (IU/L)
Hepatitis A
n=85
Hepatitis E    n=121
Co-infection(A&E)
n=6
 up to 169
65
66
0
170-180
8
6
1
181 – 540
10
45
5
>540
2
4
0

 In co-infection with HAV and HEV serum alkaline phosphatase was high in the range of 181-540 IU/L.

Table (5):
Clinical features.

Clinical features
Hepatitis A (n=85)
(%)
Hepatitis E
n=121
(%)
Co-infection(A&E)  n=6
(%)
Jaundice
85(100)
121(100)
6  (100)
Fever
45(52.9)
96 (79.3)
5 (83.6)
Pruritus
18(21.17)
83 (68.3)
4(66.6)
Fatigue
39(45.8)
89(73.4)
5(83.6)
Pain  in abdomen
16(18.8)
32(26.4)
4(66.6)
Nausea/vomiting
36(42.3)
56(46.2)
3(50)
Hepatomegaly
85(100)
121(100)
6(100)
Splenomegaly
5 (5.8)
8(6.6)
2(33.3)

Common clinical presentation with Jaundice,hepatomegaly (100%) was observed in patients followed by fever (52.9%)fatigue (45.8%) in HAV, HEV and confection with both viruses in acute viral hepatitis study group.

Table 6:Different studies in India.

Author
year
Place
No. AVH cases
Co-infection (%)
Arvind Kumar et al10
2006
Lucknow
122
30(24.6)
Monika Agrawal et al11
2016
New Delhi
475
25(5.2)
ShikhaHanda et al4
2018
Dehradun
125
13(10.4)
Gitanjalisarangi et al.15
2019
Odisha Eastern India
499
11(2.2)
Present study
2019
 Western Maharashtra
778
6(0.8)

Table shows frequency and changing trend of co-infection in different geographical areas in India.

DISCUSSION

Hepatitis A virus (HAV), and hepatitis E virus (HEV) are responsible for sporadic and epidemic forms of acute hepatitis across globe,especially common in developing countries including India. Co-infection with multiple virus in acute hepatitis is not uncommon. HAV is commonly considers as enterically transmitted etiological agent for AVH Worldwide with high seroprevalence. However, our study identified HEV high seroprevalence (15.5%) then that of HAV (10.9%) in suspected acute viral hepatitis patients. Our study results of single virus infectivity with either HAV or HEV are in concordance with different investigations from various locality in the nation, prevalence ranging from 12.6% to 78.6%.11-13   Arvindkumar et al.10 (2006) reported high rate of co-infection 24.4 % ,Monika et al.4 reported low rate of co-infection 5.2% in 2016.  Few studies are done in rural health setup, one of them was Gitanjali Sarangi et al.15 (2019) reported confection rate 2.2% in Odisha Eeastrn India. Co-infection with both HAV and HEV in present study is less (0.8%) as compare Gitanjali Sarangi et al.15 Reason may be due to low suspicion of co-infection or improved socioeconomic status and improved sanitation in recent years. .  This decreased tread in rate of co-infection (HAV & HEV) from 2006 to 2019 may be due to high prevalence of HAV antibody or vaccine against HAV and improved socioeconomic status of community in the country15.

A total of 778 number of acute viral hepatitis cases were included in the study population from July 2014 to July 2018 among which85/778 (10.9 %) positive for HAV and 121/778 (15.5%) positive for HEV. Co-infection was identified in 6/778(0.77 %). HAV high seroprevalence was noted in 16-25 years age group (44.5%), HEV seroprevalence was observed in 26-35 years age group (40.4%). Co-infection was high in 16-25 years age group. Male population have higher rate of co-infection rate (66.6%) in comparison with females (33.3%). Jaundice, fever fatigue and hepatomegaly are common clinical presentation in HAV, HEV and confection with both viruses in acute viral hepatitis.14Frequency of co-infection with HAV and HEV varies in differ studies conducted in India. Although it is known that serum alkaline phosphates level increases in acute viral hepatitis, the range is towards higher sides( above 181 IU/L) when patient having co-infection with HAV and HEV.

CONCLUSION

Our study revelled overall higher prevalence of HEV (15.5%) then that of HAV (10.9%)in suspected cases of Acute Viral hepatitis.HAV high seroprevalence was noted in 16-25 years age group (44.5%),  this show low exposure to HAV in childhood ( bellow 16 years )which result in lack of heard immunity in this age group and susceptible to hepatitis A virus  infection . HEV seroprevalence was observed in 26-35 years age group (40.4%). Co-infection was high in 16-25 years age group. There is a need for community based serosurvilance of HAV and HEV among the general population. Also there is need to strengthen the viral diagnosis laboratory at periphery. High clinical suspension in AVH patients especially among pregnant women to reduce morbidity and mortality. Health education to improving levels of personal hygiene. This study observation will help Authority to develop local policy for investigation protocol in AVH patient, also helps in future studies which are aimed to address the outcome issue in AVH patient with single virus infection / mixed viral infection. This data information will be help for planning future vaccination strategies, better implementation sanitation program, and safe water supply in this geographic area of the country.

Declarations

ACKNOWLEDGMENTS
 Authors would like to express heartfelt thanks to all participant, technical staff and clerks of laboratory for providing assistance in data collection and maintenance of documents. Author thanks to Dr. SV Kakade Associate Professor Dept. Community Medicine for application of statistical tool to for data analysis.

CONFLICT OF INTEREST
The authors declare that there is no conflict of interest.

AUTHORS’ CONTRIBUTION
RVS is principal investigator of the research project and corresponding author of the research paper. STM,  ARS, SRP  guided for design the research project and conduction of the work during study period. ADP provided Microsoft excel knowledge and its applications for assessment and data analysis.   Dr. SKP contributed for English editing of the manuscript and online submission of the research paper.

FUNDING
None.

ETHICS STATEMENT
Present study was record based. We did not require any animal experiment for the study, however the study was approved by Institutional Ethics Committee of Krishna Institute Medical sciences “Deemed to be” University Karad.

AVAILABILITY OF DATA
All datasets generated during this study are included in the manuscript.

References
  1. Khuroo MS .Study of an epidemic of non-A, non-B hepatitis – may be another possibility of human hepatitis virus distinct from post transfusion non-A, non-B type. Am J Med. 1980;68:818-824.
    Crossref
  2. Joon A, Rao P, Shenoy SM, Baliga S. Prevalence of Hepatitis A virus (HAV) and Hepatitis E virus (HEV) in the patients presenting with acute viral hepatitis. Indian J Med. Microbial. 2015;33(S1):102-105.
  3. Irshad M, Singh S, Ansari MA, Joshi YK. Viral hepatitis in India: A report from Delhi. Glob J Health Sci. 2010;2:96-103.
    Crossref
  4. Handa S, Wasim S, Karla BP, Anil R, Vipan C, Alpa G. Clinico-epidemiological profile of hepatitis A virus and hepatitis E virus co-infection in pediatric age group: a hospital based retrospective study. Int J ContempPediatr. 2019;6(2):588-592.
    Crossref
  5. Acharya SK, Madan K, Dattagupta S, Panda SK. Viral hepatitis in India. Natl Med J India. 2006;19:203-217.
  6. WHO Hepatitis A Fact Sheet Updated 2019.
  7. WHO Hepatitis E Fact Sheet Updated 2019.
  8. Das AK, Ahmed S, Medhi S, Kar P. Changing patterns of aetiology of acute sporadic viral hepatitis in India – Newer insights from North-East India. Int J Curr Res Rev. 2014;6:14-20.
  9. Naha K, Karanth S, Prabhu M, Singh MS. Dual infection with hepatitis A and E virus presenting with aseptic meningitis: A case report. Asian Pac J Trop Med. 2012;5:587-588.
    Crossref
  10. Arvind Kumar et al. Does co-infection with multiple viruses adversely influence the course and outcome of sporadic acute viral hepatitis in children? J Gastroenterol Hepatol. 2006;21:1533-1537.
    Crossref
  11. Monika Agrawal et al. A Study of Seroprevalence and Co-infection of Hepatitis A and Hepatitis E Viruses in Sporadic Cases in an Endemic Area. Journal of Medical Sciences and Health. 2016;2(3)1-5.
    Crossref
  12. Jain P, Prakash S, Gupta S, Singh KP, Shrivastava S, Singh DD, et al. Prevalence of hepatitis A virus, hepatitis B virus,hepatitis C virus, hepatitis D virus and hepatitis E virus as causes of acute viral hepatitis in North India: A hospital based study. Indian J Med Microbiol. 2013;31:261-265.
    Crossref
  13. Al-Naaimi AS, Turky AM, Khaleel HA, et al. Predicting acute viral hepatitis serum markers (A and E) in patients with suspected acute viral hepatitis attending primary health care centers in Baghdad: A one year cross-sectional study. Glob J Health Sci. 2012;4:172-183.
    Crossref
  14. Arora D, Jindal N, Shukla RK, Bansal R. Water borne hepatitis a and hepatitis e inMalwa region of Punjab, India. J ClinDiagn Res. 2013;7:2163-166.
    Crossref
  15. Sarangi G. et al.Fecal-oraltransmitted hepatitis A and E prevalence in Eastern India: A 3year retrospective study. Journal of Medical Society. 2019;33:86-90.

Article Metrics

Article View: 192

Share This Article

© The Author(s) 2020. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License which permits unrestricted use, sharing, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.