Prevalence of serological markers of hepatitis B in inflammatory bowel disease – Experience from a tertiary care centre in South India

Abstract

Inflammatory bowel disease patients are at risk of hepatitis B infection. Data on this prevalence from South Asia are limited. We conducted a prospective study comprising of 76 inflammatory bowel disease patients between October 2013 and August 2014. Prevalence of hepatitis B surface antigen in inflammatory bowel disease, ulcerative colitis and Crohn’s disease patients were 2.6%, 2.4% and 3% respectively and that of markers of hepatitis B exposure (hepatitis B surface antigen /hepatitis B core antibody) were 11.8%, 14.3% and 9.1% respectively. Risk factors found significantly more common in those positive for viral markers compared to those negative were age, non-inflammatory bowel disease related surgery and hospital admission. Only 7(9.2%) had completed hepatitis B vaccination. There is a need to create awareness among physicians regarding the importance of hepatitis B screening and vaccination in inflammatory bowel disease patients.

Keywords

Inflammatory bowel disease hepatitis B serology vaccination

Introduction

Inflammatory bowel disease (IBD) covers idiopathic chronic intestinal inflammation. Although a significant gastrointestinal problem in high-income countries for several decades, it is now being increasingly diagnosed in Asia including India. This may be due to increased awareness and improvements in diagnostic modalities.¹ Traditionally, mesalamine and steroid compounds have been used to manage IBD. More recently, immunomodulator drugs and biological agents have been added to the therapeutic armamentarium.

Various infections including viral infections have been associated with IBD, one being hepatitis B infection.² Chronic hepatitis B infection, which affects more than 350 million people worldwide, can result in cirrhosis and hepatocellular carcinoma.³ India is considered an area of intermediate prevalence.⁴ Although an effective vaccine exists, its coverage in India is suboptimal.⁵

With increasing use of immunosuppressive therapy in IBD, reactivation of hepatitis B is possible.^6–8 Data show that hepatitis B vaccination coverage in patients with IBD is low.^9–11 The seroprotection offered by immunisation with standard doses of hepatitis B vaccine in IBD is also found to be suboptimal.^12–14

Major guidelines on hepatitis B management strongly recommend testing for hepatitis B markers prior to initiating cytotoxic chemotherapy or highly immunosuppressive treatments.^15,16 The European Crohn’s and Colitis Organisation guideline advises treatment for those positive for chronic hepatitis B infection with anti-viral agents, starting two weeks prior to the onset of immunosuppressive therapy and extending up to 12 months of their cessation.¹⁷ On the other hand, vaccination is recommended for all those who are seronegative.¹⁷ Unfortunately, compliance with these recommendations has been poor.¹¹ Data on the burden of hepatitis B infection in those with IBD especially from South Asia are limited and reported figures vary across studies.^18–21

The aims of our study were to determine the prevalence of serological markers of hepatitis B exposure in patients with IBD attending a tertiary care centre in South India and their hepatitis B vaccination status.

Methods

Ours was a prospective study conducted between October 2013 and August 2014 in our institution. We recruited IBD patients (diagnosed as ulcerative colitis, Crohn’s disease or IBD-unclassified) who agreed to participate after obtaining written informed consent. Their demographic, historical, clinical, medication, treatment, biochemical, endoscopic, histologic and radiological details were collected through direct interviews at the outpatient clinic or as inpatients and from the hospital information system. The Montreal classification was utilised to categorise the patients into various clinical phenotypes.²² A detailed questionnaire was utilised to assess the risk factors for hepatitis B transmission and vaccination status for hepatitis B.

All recruited patients were tested for hepatitis B surface antigen (HBsAg). Those found negative were tested for antibodies to hepatitis B core protein (anti-HBc). Any patient found positive for serological markers of hepatitis B underwent further evaluation and management. Other investigations done included antibodies to hepatitis C virus (anti-HCV) and human immunodeficiency virus (HIV), liver function tests and imaging for evidence for chronic liver disease. Those positive for HBsAg were additionally tested for quantitative hepatitis B virus (HBV) DNA level and ‘e’ antigen (HBeAg) status.

The sample size for our study was calculated to be 76 based on 20% prevalence of anti-HBc, confidence level of 0.95 and precision level of 9%.^23–25

Results were analysed using SPSS version 16. Mean, median, standard deviation (SD), range and proportions were calculated as appropriate. Categorical variables were analysed using χ² test or Fisher’s exact test as applicable while continuous data were analysed using Mann–Whitney U test or unpaired t test as applicable. A ‘p’ value < 0.05 was considered statistically significant.

Our study was approved by the Institutional Review Board & Ethics Committee of our hospital (IRB Min. No. 8316 [OBSERVE] dated 18.06.2013).

Results

A total of 76 patients was recruited for the study, of whom 42 (55.3%) had ulcerative colitis, 33 (43.4%) Crohn’s disease and one patient unclassified IBD. Their mean age was 37.5 ± 13.9 years while the male: female ratio was 1.7:1. The majority came from the following states: West Bengal: 25 (32.9%); Tamil Nadu: 16 (21.2%); Jharkhand: 13 (17.1%); Andhra Pradesh: 8 (10.5%). An urban background was seen in 44 (58%). Table 1 depicts the patients’ baseline characteristics according to their respective subgroups.

Table 1.

Baseline characteristics of the study patients.

	Ulcerative colitis (n = 42)	Crohn’s disease (n = 33)	IBD – unclassified (n = 1)
Mean age (SD) in years	39.8 (12.9)	34.3 (14.7)	48
Median total duration (range) in months	27.5 (1–410)	36 (2–328)	7
Duration prior to diagnosis (range) in months	6 (1–180)	20 (2–228)	5
Male: Female	26 (61.9%)/16 (38.1%)	22 (66.7%)/11 (33.3%)	0/1
Habitat: urban /rural	21 (50.0%)/21 (50.0%)	22 (66.7%)/11 (33.3%)	1/0
Surgery related to IBD	2 (4.8%)	8 (24.2%)
Medications (anytime)
Mesalamine	42 (100%)	32 (97%)	1
Steroids	28 (66.7%)	10 (30.3%)	1
Azathioprine	18 (42.9%)	13 (39.4%)	0
Methotrexate	0 (0%)	2 (6.1%)	1
Antibiotics	7 (16.7%)	7 (21.2%)	0
Montreal classification:	Extension	Age at diagnosis
	E1: 7 (16.7%)	A1: 7 (21.2%)
	E2: 15 (35.7%)	A2: 20 (60.6%)
	E3: 20 (47.6%)	A3: 6 (18.2%)
		Location
		L1: 10 (30.30%)
		L2: 4 (12.12%)
		L3: 19 (57.57%)
		L4: 0 (0)
		Behaviour
		B1: 14 (42.42%)
		B2: 14 (42.42%)
		B3: 5 (15.15%)

IBD: inflammatory bowel disease.

Table 2 depicts the frequencies of hepatitis B markers in the study population. None of the patients positive for hepatitis B markers had features of chronic liver disease nor portal hypertension. The two patients who were positive for HBsAg were taking anti-viral therapy. Both were negative for HBeAg and had low (12 IU/mL) or negative HBV DNA levels. All patients were negative for antibodies against HCV and HIV.

Table 2.

Prevalence of hepatitis B markers in the study population.

	Ulcerative colitis (n = 42)	Crohn’s disease (n = 33)	IBD – unclassified (n = 1)	p value^#
HBsAg + ve	1/42 (2.4%, 95% CI: 0.4–12.3%)	1/33 (3%, 95% CI: 0.5–15.3%)	0/1 (0)	1.000
Anti-HBc + ve	5/41 (12.2%, 95% CI: 5.3–25.5%)	2/32 (6.3%, 95% CI: 1.7–20.2%)	0/1 (0)	0.456
Hepatitis B markers (HBsAg/Anti-HBc + ve)	6/42 (14.3%, 95% CI: 6.7–27.8%)	3/33 (9.1%, 95% CI: 3.1–23.6%)	0/1 (0)	0.723

CI: confidence interval.

#Comparison between ulcerative colitis and Crohn’s disease patients.

Multiple risk factors were compared between those who were positive and negative for hepatitis B markers (Table 3). Mean age (p = 0.034), non-IBD related surgery (p = 0.009) and non-IBD related hospital admission (p = 0.008) were significant risk factors.

Table 3.

Risk factors related to markers of hepatitis B infection.

	Negative viral markers (n = 67)	Positive viral markers (n = 9)	p value
Mean age (SD)	36.3 (13.9)	46.7 (10.2)	0.034*
Male gender	43 (64.2%)	5 (55.6%)	0.718
Habitat (rural)	31 (46.3%)	1 (11.1%)	0.071
Parenteral injections	66 (98.5%)	9 (100%)	1.000
Dental procedures	14 (20.9%)	0 (0)	0.197
Surgery (IBD)	10 (14.9)	0 (0)	0.597
Surgery (non-IBD)	9 (13.4%)	5 (55.6%)	0.009*
Hospital admissions (IBD related)	28 (41.8%)	4 (44.4%)	1.000
Hospital admissions (non-IBD related)	14 (20.9%)	6 (66.7%)	0.008*
Transfusions	14 (20.9%)	2 (22.2%)	1.000
Parenteral drug abuse	0 (0)	1 (11.1%)	0.118
High risk sexual behaviour	1 (1.5%)	0 (0)	1.000
Tattooing	1 (1.5%)	0 (0)	1.000
Piercing	21 (31.3%)	4 (44.4%)	0.465
Sharing of household articles^#	3 (4.5%)	2 (22.2%)	0.104
Steroids	35 (52.2%)	4 (44.4%)	0.733
Azathioprine	30 (44.8%)	1 (11.1%)	0.074
Methotrexate	3 (4.5%)	0 (0)	1.000
Family history of hepatitis B	0 (0)	0 (0)	–
Maternal history of hepatitis B	0 (0)	0 (0)	–
Hepatitis B in partner	0 (0)	0 (0)	–
Health care worker	2 (3%)	0 (0)	1.000

IBD: inflammatory bowel disease.

#Potentially infectious like toothbrushes, razors, towels, etc.

Out of 76 patients studied, only 7 (9.2%, 95%CI: 4.5–17.8%) patients had completed three doses of vaccination against hepatitis B. Of these, six were negative for hepatitis B markers while one tested positive for anti-HBc.

Discussion

Most available published studies on the seroprevalence of hepatitis B in IBD are from Western countries and East Asia.^{8,9,18,19,21,26–34} Seroprevalence of markers for either current or previous hepatitis B infection in our cohort was not significantly different between ulcerative colitis and Crohn’s disease (Table 2). Variations across various studies could be due to differences in the local prevalence of hepatitis B, risk factors for hepatitis B infection, age of study subjects, vaccination policies and implementation.^27,30

Assessing the presence of both HBsAg and anti-HBc markers in IBD patients has a bearing on the need for anti-viral therapy when immunosuppressive therapy is considered to prevent a flare of hepatitis B infection. For those who are HBsAg positive, anti-viral agents should be initiated prior to start of immunosuppressive therapy and continued for at least a year after its cessation. IBD patients who are positive only for anti-HBc should be assessed for viremia (HBV DNA) every 2–3 months, with anti-viral drugs being given if HBV-DNA is detected.¹⁷

Other studies of major risk factors included family history of hepatitis B, moderate-to-severe disease, older age, previous IBD related admissions, low platelet count and biological agents.^{9,19,28,33,34} Family history suggests sharing of personal and household articles and through sexual contact.^35,36 Older age suggests a longer disease duration which increases the risk of contracting hepatitis B.²⁸ Moderate-to-severe IBD may lead to increasing need for IBD related admissions, parenteral injections and surgery.

Interestingly, we found significant association with non-IBD related hospital admission or surgery indicating that these may well be opportunities for viral transmission. Improper sterilisation and reuse of sharp instruments, frequent and unwarranted parenteral injections, substandard blood bank facilities and lack of awareness of infection control in primary and secondary health settings may therefore significantly contribute to increased risk of hepatitis B.^37,38

Hepatitis B vaccination is deemed effective when the anti-HBs titre is >10 mIU/mL (in the absence of anti-HBc) tested 1–2 months after the last dose of vaccine. Effective vaccination in patients with IBD was observed to be between 22% and 76% across various studies.^{19,21,27,29–31,39–41} If a higher cut-off of anti-HBs titre >100 mIU/mL was considered, the efficacy rate dropped down to as low as 12%.⁹ As we found only 9.2% of our cohort had completed the full three doses of vaccination, this is important although we did not specifically check anti-HBs titres in these patients. Despite the potential risk factors for hepatitis B infection in IBD and recommendations from different societies, vaccination is often under-prescribed.^10,11

A limitation of our study was the relatively small sample size in comparison to other studies and it coming from a single tertiary care centre in South India. Also, we could not test anti-HBs and HBV DNA in the entire IBD study population owing to resource constraints.

In conclusion, the prevalence of serological markers of hepatitis B exposure in our study population with IBD was 11.8%. Older age, history of non-IBD related admission and non-IBD related surgery were significantly associated with positivity for hepatitis B markers. Hepatitis B vaccination rate in our population was very low (9.2%). There is a need to create awareness among physicians regarding the importance of hepatitis B screening and vaccination in IBD patients.

Footnotes

Acknowledgements

We would like to acknowledge Dr Ashish Goel (Professor, Department of Hepatology, Christian Medical College, Vellore), Dr Anna B Pulimood (Professor, Department of Pathology, Christian Medical College, Vellore) and Dr Priya Abraham (Professor, Department of Clinical Virology, Christian Medical College, Vellore) for their kind support towards the conduct of this study. This scientific work was done as part of Dr Amol Prabhakar Patil’s Master’s thesis as required for the DM (Gastroenterology) examination of the Tamil Nadu Dr. MGR Medical University, Chennai, India held on August 2015. It was presented as a poster at the 55th Annual Conference of the Indian Society of Gastroenterology (19–23 December 2014) held in Mumbai, India.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Ebby George Simon

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