Beginnings of the World Hepatitis Day Commemorations
The discovery of the Hepatitis B virus followed a couple of years later by the first hepatitis B vaccine were landmark moments in clinical infectious diseases practice, which led the Nobel Prize committee for physiology and medicine to bestow its award for 1967 to the person behind the two discoveries: Dr Baruch Blumberg. To further enshrine his contribution, the world hepatitis day is celebrated on his birthday, 28th July.
The Global Impact of Hepatitis
While there are various infectious and non-infectious causes of hepatitis, the widespread epidemiology of infectious hepatitis places it as one of the foremost reasons for infectious diseases consultations. More than 2.3 billion people globally (one out of four people) are infected with one or more hepatitis viruses. The World Health Organization (WHO) estimates that 354 million people worldwide are living with a viral hepatitis infection, with more than 1.4 million deaths per year. Lack of knowledge on the illness, diagnostic limitations, global inequity in distribution of therapeutic drugs and lack of access to vaccines, and in particular birth dose of hepatitis B vaccine are major contributing factors to the continuing spread of hepatitis. In sub-Saharan Africa, which is endemic for most viral hepatitis infections (where 4.3 million of the 6 million children living with chronic hepatitis B infection were living in 2019), only 14 countries had introduced a birth dose of hepatitis B vaccine into their programs in 2021. Further to infectious morbidity and mortality, hepatitis B and C in particular have oncogenic potential with chronic hepatitis B being the leading cause of liver cancer.
View From a Hepatitis A Endemic Country
While globally, hepatitis E has taken over as the leading cause of infectious hepatitis in countries with a long history of practicing joint hepatitis A and hepatitis B vaccination programs, nations like my country Ethiopia still observe high prevalence for the two infections.
While benign and mostly a self-limiting illness in children, hepatitis A causes large outbreaks in daycare centers and primary schools. The WHO estimated in 2019 that more than 2 billion individuals globally lack safe water and more than 4 billion did not have adequate sanitation. Such observations make the control of orofecally transmitted infections like hepatitis A challenging. Alternatively, the introduction of inactivated hepatitis A vaccines among children have led to annual reduction of cases by 67% - a figure which exceeded by ten folds than pre-vaccine efforts in countries like Brazil. Immune-protection extends to 10 years (one-dose) to 15 years (two-doses). While the WHO recommends the inclusion of hepatitis A vaccines in endemic countries, only 26 countries worldwide had introduced them into their immunization programs by 2020 – with no south Asian or sub-Saharan country among them.
Are Our Multi-valent Hepatitis B Vaccines Failing Us?
Hepatitis B accounts for two-thirds of the annual viral hepatitis-related mortality around the world. It is transmitted through infected blood or body fluids (needles, household exposure, perinatal, horizontally through household or school exposure etc) with the highest risks reserved for a high degree of exposure, acute source infection and positive source HBe antigen. Perinatal transmission occurs more efficiently during delivery rather than in-utero. The highest incidences are observed in east European, south and south-east Asian and African countries where infection control faces difficulties of low antenatal testing rates and low rates of post-exposure prophylaxis. Estimates though are grossly under-reported with serologic diagnostic limitations hampering a true understanding of acute and chronic infection as well as vaccine efficacy. The latter problem is one which has garnered little attention. Multiple studies from all corners of Ethiopia, a country with a three-dose hepatitis B vaccine schedules for infants (and no birth dose introduced yet) show serologic evidence of immune-protection (anti-hepatitis B surface antibodies of 10 IU/ml or more) in three-fourth of children beyond the age of 8 – 9 years. These findings are also reflected in other sub-Saharan countries like Senegal. Whether these observations are due to a drop in efficacy of the pentavalent (DPT-Hib-hep B) vaccine administered in these countries, the presence of many acquired immune-compromising comorbidities or indeed the lack of birth dose vaccine administration begs further studies to be conducted as they have wide-reaching implications in long-term prevention of hepatitis B and by extension, its dependent – hepatitis D infection. Major barriers to treatment are absence of therapeutic drugs for chronic hepatitis B from public hospital formularies and a lack of public funding and commitment to correct the gap.
It is High Time for Widespread Hepatitis C Screening
Hepatitis C infection remains a public health concern, in particular in developing countries where estimates especially in children and pregnant women are underestimated. Wider screening is warranted especially among siblings of children with vertically acquired hepatitis C infection, children with congenital or acquired immune-suppression and all those with elevated serum alanine transaminase (ALT) levels. Untreated infections in adults lead to cirrhosis and liver cancer and in the case of pregnant women, fetal transmission. The most common route for pediatric infection is mother-to-newborn transmission with risk of transmission ranging from 5 – 6% in immune-competent mothers to as high as 25% in mothers co-infected with HIV. While routine screening during pregnancy has proved cost-effective in high-income settings, it may prove an even more useful component of antenatal care in endemic regions as most infections remain asymptomatic. This is particularly important as molecular tests which reliably detect early infancy diagnosis are not widely available and the performance of newborn and infant serologic testing is impaired by the failure of maternal antibodies to clear till 18 months of age. The treatment scope of hepatitis C is one of the most dynamic areas of infectious diseases. We now have effective treatment for all patients aged 3 years and older and studies on treatment options for even younger children are the next frontier.
Hepatitis E: A Neglected Public Health Concern
With increasing hepatitis A and hepatitis B vaccination programs, hepatitis E is coming to the forefront as a leading cause of viral hepatitis. Over 20 million new infections and more than 70,000 deaths are recorded annually due to hepatitis E. Complications (especially neurologic) are more common in immune-suppressed individuals, and pregnant women and those with preexisting chronic liver disease. Even though, an effective vaccine has been licensed in China more than a decade ago, limited knowledge on the epidemiology of hepatitis E and even during recognized outbreaks, unclear vaccine supply chains have limited widespread immune-prophylaxis, in particular for those with pre-existing liver disease. There are though knowledge gaps of the efficacy and safety of the vaccine among the remaining vulnerable populations (pregnant women, immune-compromised people) and children aged 16 years and younger.
The future offers many opportunities for research into new drugs, vaccine studies, and the design of screening programs and casting a wider net to improve care of vulnerable populations for acute and chronic hepatitis. Four of the five major types of viral hepatitis (A up to E) are now vaccine-preventable. This year’s world hepatitis day offers a reflection point for us to do more to reverse the landscape of one of the commonest infectious syndromes.
By Tinsae Alemayehu, ISID Emerging Leader, Ethiopia
Honorary Associate Professor, Pediatric Infectious Diseases
Department of Pediatrics & Child Health, St. Paul’s Hospital Millennium Medical College
Pediatric Infectious Diseases Specialist, American Medical Center
Addis Ababa, Ethiopia