Frequency of Hepatitis C Infection in Children with Β-Thalassemia Major

INTRODUCTION:

β- Thalassemia major is a severe hereditary haemoglobin disorder caused by mutation of the b-globin gene with the results of ineffective erythropoiesis, severe anaemia, and life-long reliance on regular blood transfusion starting in early childhood.1 Worldwide, hemoglobinopathies are one of the most common monogenic disorders with about 60,000 affected births annually, and a significant concentration in the Mediterranean region, Middle East and South Asia.2 Pakistan is in a thalassemia belt with the estimated carrier rate of 5-7%, and thousands of affected births each year constituting a major public health challenge in paediatric population.3

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide, affecting an estimated 58 million individuals, with ongoing transmission leading to new infections each year.4 Although the prevalence in children is lower than that in adults, infection in children is of clinical significance as the majority of infected children will develop chronic infection with possible long-term hepatic sequelae.5 Pakistan has one of the highest HCV burdens worldwide and prevalence estimates range between 4-8% on national level therefore it carries significant public health implications, especially in susceptible children groups.6

Children with beta-thalassemia major are more prone to HCV infection because of repeated exposure to blood transfusions, especially in countries where optimal donor screening and testing for nucleic acids are not routinely performed.7 To investigate this phenomenon, studies conducted in developing countries have reported significantly higher HCV prevalence among multi-transfused thalassemic children which in some instances exceeds that of the general pediatric population.8 Chronic HCV infection in these patients can lead to more rapid hepatic fibrosis due to synergism of the effects of excess iron and liver injury contributed by viral infections with the risk of turning into cirrhosis and hepatocellular carcinoma.9 In spite of improvements in transfusion safety, HCV remains one of the most common transfusion-transmitted infections among children with transfusion-dependent thalassemia in high-burden countries.10

Given the high prevalence of beta-thalassemia major and high national burden of HCV infection in Pakistan, it is important to know the frequency of hepatitis C infection in transfusion-dependent children. Local epidemiological data is needed to measure the success of blood screening programmes, pinpoint gaps in transfusion safety and define preventive strategies. Establishing the magnitude of this problem will help to inform healthcare policies with a goal to reduce transfusion-transmitted infections and improve the long-term outcomes in this vulnerable pediatric population.

MATERIALS AND METHODS:

This Study was a cross-sectional study and was performed at the department of pediatric medicine as Sir Ganga Ram Hospital Lahore between May 30, 2025 and October 29, 2025 following approval from the institutional ethical review committee. The sample size of 138 patients was calculated at 95% confidence level, 8% margin of error with anticipated frequency of hepatitis C virus (HCV) infection of 31.7% in patients with b-thalassemia major based on previously reported data.¹¹ A non-probability consecutive sampling technique was employed for participant recruitment.

Children of both sexes (3-13 years) diagnosed with beta-thalassemia major according to the operational criteria and transfusion dependent (transfusion of blood two to three times per month) were recruited. Patients were excluded if they had pre-existing hepatic disease (ALT or AST levels >45 U/L), pre-existing renal disease (serum creatinine >1 mg/dL), thrombocytopenia (platelet count <100,000/mm³), neutropenia (polymorphonuclear leukocyte count <1,500/mm³), very severe anemia (hemoglobin <5 g/dL) or evidence of bone marrow suppression, known hypersensitivity to hydroxyurea or current treatment with chemotherapy or radiotherapy.

Writing informed consent obtained from parents or legal guardians, eligible patients were enrolled consecutively until the required sample size was attained. Demographic information such as age and gender was recorded on a structured predesigned proforma. An approximately 3-5 mL of venous blood was collected under aseptic condition and was collected in sterile serum bottles. Samples were examined at the hospital laboratory for identification of anti-HCV antibodies in a third generation enzyme linked immunosorbent assay (ELISA). All samples which tested positive in anti-HCV antibodies were submitted for confirmatory polymerase chain reaction (PCR) testing for detection of HCV RNA.

Data was transcribed and analysed with Statistical Package for the Social Sciences (SPSS) version 27.0. Qualitative variables, such as gender, socio-economic status and HCV infection status, were summarised as frequencies and percentages. Quantitative variables including age and time of illness were represented as mean+-SD. Stratification was done for age, gender, socio-economic status, and duration of illness to control for possible effect modifiers. Post stratification the Chi-square was used to identify the associations between categorical variables. A p-value <0.05 was regarded as statistically significant.

RESULT:

A total of 138 children with β-thalassemia major were included in the study. Among them, 81 (58.7%) were males and 57 (41.3%) were females, showing a male predominance. Regarding age distribution, 45 (32.6%) children were aged 3–5 years, 47 (34.1%) were between 6–10 years, and 46 (33.3%) were between 11–13 years. The mean age of the participants was 8.01±3.56 years.

With respect to socio-economic status, the majority of patients, 84 (60.9%), belonged to the low socio-economic group, followed by 51 (37.0%) from the middle socio-economic group, while only 3 (2.1%) were from the high socio-economic class. Regarding duration of illness, 93 (67.4%) children had illness duration of less than 24 months, whereas 45 (32.6%) had illness duration of 24 months or more. The mean duration of illness was 21.74 ± 4.37 months. Hepatitis C infection was detected in 43 (31.2%) children, while 95 (68.8%) were negative for hepatitis C virus infection.

Table-2 shows the stratification of hepatitis C infection with respect to gender, age groups, socio-economic status, and duration of illness. Hepatitis C showed no significant association with gender (p = 0.114) or age group (p = 0.218). However, a significant association was observed with socio-economic status (p = 0.011) and duration of illness (p = 0.001), with higher HCV positivity among children from low socio-economic status and those with illness duration ≥24 months.

Table-1: Frequency distribution of different variables (n=138)

Variables		Frequency	Percent
Gender	Male	81	58.7%
Gender	Female	57	41.3%
Age groups	3-5 years	45	32.6%
	6-10 years	47	34.1%
	11-13 years	46	33.3%
	Mean age (years)	8.01±3.56
Socio-economic status	Low	84	60.9%
	Middle	51	37.0%
	High	3	2.1%
Duration of illness	<24 months	93	67.4%
	≥24 months	45	32.6%
	Mean duration of illness (months)	21.74±4.37
Hepatitis C	Yes	43	31.2%
Hepatitis C	No	95	68.8%

Table-2: Stratification of hepatitis C with respect to different variables

Variables		Hepatitis C		p-value
Variables		Yes	No	p-value
Gender	Male	21(25.9%)	60(74.1%)	0.114
Gender	Female	22(38.6%)	35(61.4%)	0.114
Age groups	3-5 years	10(22.2%)	35(77.8%)	0.218
	6-10 years	15(31.9%)	32(68.1%)
	11-13 years	18(39.1%)	28(60.9%)
Socio-economic status	Low	34(40.5%)	50(59.5%)	0.011
	Middle	9(17.6%)	42(82.4%)
	High	0(0.0%)	3(100.0%)
Duration of illness	<24 months	17(18.3%)	76(81.7%)	0.001
Duration of illness	≥24 months	26(57.8%)	19(42.2%)	0.001

DISCUSSION :

In the present study the prevalence of hepatitis C virus (HCV) infection among children with beta-thalassemia major was 31.2%. This figure is still of concern despite an improvement in the protocols for blood screening. Recent regional and international data have shown variable but persistently high HCV rates in transfusion-dependent patients with thalassemia.

A Pakistani study found that HCV prevalence in b-thalassemia major patients was 25.7%, while a systematic review in 2022 found a higher prevalence of HCV frequency 34.7%.^{12 - 13} Likewise, a study in India found HCV seropositivity in 30.5% of transfusion-dependent children.¹⁴ These results are similar to ours indicating that HCV remains a significant burden in thalassemia populations.

Internationally, prevalence rates differ depending on the screening strategies and healthcare infrastructure. An Indian study published in 2024 found HCV infection in 32.1% of the multi-transfused thalassemia patients which is close to our result. A higher prevalence of 44.0% was documented by a study from Egypt in 2024 which may reflect differences in transfusion safety measures.^15-16

Conversely, lower rates have been reported in countries where the rate of nucleic acid testing (NAT) has been implemented; for instance, a 2021 study in Iraq reported 18.6% prevalence, and data from a cohort study in Turkey (2023) showed only 12.4% HCV positivity.^17-18 Such disparity is likely due to differences in blood donor screening practises, NAT implementation and infection control measures.

Our study also showed the significant association between longer duration of illness (24 months) and HCV positivity (57.8% vs. 18.3%, p=0.001), consistent with the findings of a study in Bangladesh, showing persistence of HCV infection (52.0% HCV positivity) among patients transfused for >18 months.¹⁹

Similarly, low HCV rates (3.1%) were recorded in a 2023 study in Yemen in patients with transfusion dependent.²⁰ Another finding in our study is an association between low socio-economic status and HCV infection (40.5%, p=0.011), with a 2025 study in amongst excentre centers on socio-economic deprivation, which found association of low socio-economic deprivation as an independent predictor for transfusion-transmitted infections.²¹

Despite improved screening of donors, continuous HCV-associated infection among beta-thalassemia major patient’s highlights lags in transfusion safety and early antiviral therapy. The prevalence observed in our study (31.2%) translates to an intermediate-to-high burden when compared with both regional and international data and raises awareness necessary for the continued vulnerability of multi-transfused children in resource-limited settings.

This study was done in a single tertiary care centre with a relatively small sample size, which may have limited generalizability. In addition, no viral load quantification or genotype analysis was performed and risk factors, such as number of transfusions, were not analyzed in detail.

CONCLUSION :

A high frequency of hepatitis C virus infection was seen among children with beta-thalassemia major, specifically among those children with longer duration of illness and low socio-economic status. Strengthening transfusion screening and prevention approaches is necessary to lessen the burden of disease.

BIBLIOGRAPHY:

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Frequency of Hepatitis C Infection in Children with Β-Thalassemia Major

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