A prospective observational study conducted in Karachi, Pakistan, has found that the hepatitis E vaccine Hecolin was safe and well tolerated among 375 non-pregnant women of childbearing age, with only mild, transient adverse effects reported over a 21-day follow-up period. The research, published in the Egyptian Liver Journal, addressed a gap in safety data for a vaccine that could protect a group at disproportionately high risk from hepatitis E virus infection in endemic regions.
Hepatitis E virus is a non-enveloped, positive-sense RNA virus of the genus Orthohepevirus and a major cause of acute viral hepatitis worldwide, particularly in low- and middle-income countries with poor sanitation and limited access to clean water. An estimated 19 to 20 million HEV infections occur globally each year, producing millions of symptomatic cases and tens of thousands of deaths, with a heavy disease burden across sub-Saharan Africa and South and East Asia. Genotypes 1 and 2 are restricted to humans, spread through contaminated water, and drive large outbreaks in endemic areas, while genotypes 3 and 4 are zoonotic and transmitted via contaminated food and water or undercooked meat from infected animals.
In Pakistan, where the virus is endemic, pooled seroprevalence in the general population has been estimated at 23.8 percent. Infection during the third trimester of pregnancy is associated with increased rates of fulminant hepatic failure, maternal mortality, and adverse fetal outcomes, making pregnant women a particularly vulnerable group. Hormonal changes, altered immune responses, and viral factors are thought to contribute to severe courses in pregnancy. The Hecolin vaccine, a recombinant HEV239 vaccine licensed in China, is given as a three-dose intramuscular series at 0, 1, and 6 months and is approved for adults, including women of childbearing age, but uptake remains limited by low awareness, poor accessibility, and weak integration into maternal health programs.
The study was carried out at the Gastroenterology Department of Jinnah Postgraduate Medical Centre, a tertiary care hospital, and Atiya General Hospital between September 2023 and September 2025. Using non-probability convenience sampling, the researchers approached 600 eligible women during routine outpatient or inpatient visits; 375 consented and received at least one vaccine dose. Participants were non-pregnant women aged 16 to 43 years without comorbidities, with no prior hepatitis E vaccination, and without contraindications to vaccination. Women who were pregnant at baseline, had chronic liver disease, or were immunodeficient were excluded. The sample size requirement of 278 participants had been calculated with OpenEpi based on the reported 23.8 percent HEV prevalence, a 95 percent confidence level, and a 0.05 margin of error.
Participants were stratified into two age groups, 16 to 22 years and 23 to 43 years, to assess whether demographic characteristics and post-vaccination adverse effects differed between them. The vaccine was administered free of charge by trained healthcare professionals under aseptic conditions according to the manufacturer’s guidelines. Follow-up assessments were conducted on Day 1, Day 7, and Day 21 after vaccination using a structured questionnaire prepared in English and translated into Urdu, with responses collected through face-to-face interviews. Data were analyzed with SPSS version 26.0 using descriptive statistics and Chi-square tests, with a p-value of 0.05 or less considered statistically significant.
The mean age of participants was 24.47 years with a standard deviation of 5.44 years, and the cohort was almost evenly split between the two age strata, with 186 women aged 16 to 22 and 189 aged 23 to 43. Most participants were unmarried, 303 of 375, and nearly all, 369 or 98.4 percent, resided in Sindh province. Students made up 39.5 percent of the cohort and housewives 24.8 percent, with smaller proportions of caretakers, teachers, office workers, laborers, and doctors. Only 19 participants, 5.1 percent, reported known allergies.
Adverse effects were mild, infrequent, and concentrated at the first follow-up visit. On Day 1, flu-like symptoms were reported by 18 participants, 4.8 percent, and fever by 14, or 3.7 percent, while headache affected 1.9 percent and a single participant reported cold sores. By the second and third follow-ups, complaints had fallen to a minimum, with only 8 cases of flu-like symptoms, 2.1 percent, and one headache reported, and 366 participants, 97.6 percent, reporting no side effects at all. No serious adverse events occurred at any point, and differences in adverse effects between the two age groups were not statistically significant. The authors noted that the single case of herpes labialis has no established biological mechanism linking it to the HEV239 vaccine and was more plausibly incidental than vaccine-attributed.
The age stratification revealed expected demographic contrasts rather than safety differences. Mean age differed significantly between the groups, at 20.26 years in the younger group and 28.60 years in the older group. Older participants were more likely to be married, 65 of 189 compared with 7 of 186, and to work as housewives or in professional occupations, whereas younger participants were predominantly students, 119 versus 29. Province of residence and allergy history showed no significant association with age group. The authors emphasized that vaccine safety was consistent across both strata.
The findings align with an established international evidence base. In a phase 4 trial in Matlab, Bangladesh, 19,460 non-pregnant women received either HEV239 or a hepatitis B vaccine; HEV239 was well tolerated with only mild adverse effects and no vaccine-related serious events, although a slightly higher miscarriage rate was observed among participants who became pregnant compared with controls, a risk the Karachi study cannot address because pregnant women were excluded by design. Other trials in adults aged 16 to 39 years and healthy US adults similarly reported mild, short-lived reactions and no vaccine-related severe adverse events. A meta-analysis of recombinant HEV vaccine trials found the vaccine highly effective in preventing hepatitis E, with more local reactions such as injection-site pain and bruising than controls but no significant difference in systemic or serious adverse events.
The study’s limitations are substantial and acknowledged by the authors. Follow-up lasted only 21 days, so the study cannot speak to antibody persistence or long-term protection, and participants did not undergo systematic serologic testing to confirm seroconversion. Adverse effects were self-reported, raising the possibility of underreporting or failure to detect late-onset effects, and findings may not generalize to pregnant women. The authors conclude that hepatitis E vaccination is safe, well tolerated, and acceptable among non-gravid women of childbearing age in an endemic setting, findings they say support integrating the vaccine into public health programs, while further studies should assess duration of protection, safety and immunogenicity during pregnancy, and strategies to increase vaccine coverage.
Subject of Research: Safety and tolerability of the Hecolin hepatitis E vaccine in non-pregnant women of childbearing age in Pakistan
Article Title: Hepatitis E vaccination in women of childbearing age: safety and tolerability outcomes
Article References: Butt, N., Idris, O., Shahid, B., Zafar, S., Talpur, M. F. A., & Kamani, L. (2026). Hepatitis E vaccination in women of childbearing age: safety and tolerability outcomes. Egyptian Liver Journal, 16(1), Article 66. https://doi.org/10.1186/s43066-026-00554-z
Image Credits: AI Generated
DOI: 10.1186/s43066-026-00554-z
Keywords: hepatitis E, Hecolin vaccine, HEV239, vaccine safety, women of childbearing age, Pakistan, observational study, adverse effects, public health, viral hepatitis, Karachi, immunization
News Source: Kristina Jarvis. (October 29, 2026). Hepatitis E Vaccine Well Tolerated in Women of Childbearing Age. Scienmag.
