Chronic infection with hepatitis B virus (HBV) affects approximately three hundred million people worldwide. Under current international guidelines, most of these people with chronic hepatitis are not eligible for antiviral therapy, because the evidence to expand treatment eligibility to these asymptomatic people living with HBV in Africa is very scarce.
A new study conducted by the Hepatitis Research Group at the Medical Research Council Unit-The Gambia at the London School of Hygiene and Tropical Medicine (MRCG at LSHTM), in collaboration with Gambia Government partners, Imperial College London, Institut de Recherche en Santé de Surveillance Épidemiologique et de Formation (IRESSEF) and Institut Pasteur Paris, analysed the clinical outcomes of ineligible and untreated adults with chronic HBV infection enrolled in the PROLIFICA cohort study in The Gambia. This study published in The Lancet Gastroenterology and Hepatology, addresses the critical knowledge gap around the need to expand antiviral therapy among these asymptomatic adults in Africa.
“Understanding the natural history of chronic hepatitis B in Africa is crucial for shaping treatment guidelines and so far, data on death or liver complications among untreated adults are scarce in Africa,” Dr. Gibril Ndow, lead author of the study confirmed.
“Our findings suggest that in The Gambia, the 6-year risk of death or developing liver cancer in people who are not eligible for antiviral therapy is very low. The clinical benefit of expanding treatment to this sub-group of patients is therefore uncertain and needs further study with a longer follow-up period,” he said.
The PROLIFICA cohort study recruited 943 adults with chronic HBV in The Gambia between December 2011 and January 2014 and of these, 806 individuals who were deemed ineligible for antiviral therapy at baseline, were monitored over a median follow-up of 6 years. The study found that adults with hepatitis B who were not eligible for treatment at diagnosis did not die at a higher rate compared to the general Gambian adult population.
Having liver disease at diagnosis (cirrhosis), being co-infected with hepatitis C, or having high blood pressure, were factors associated with death among people with hepatitis B. During this follow-up period, none of the people with hepatitis B, who were ineligible for treatment at diagnosis, developed liver cancer or decompensated cirrhosis. However, 7% had disease progression, either in the form of becoming newly eligible for treatment or having an increase in their liver stiffness (fibrosis). The study found that the amount of virus present in the blood at diagnosis (HBV viral load) was the main predictor of disease progression.
“These results provide important evidence that should be taken into account in the increasing debate of whether all individuals with chronic hepatitis B in Africa should be treated. Our results show that people living with chronic hepatitis B who have no, or mild liver disease hardly progress and mainly die from non-liver related causes, with high blood pressure being an important risk factor of death in our study population,” Professor Maud Lemoine, senior author of this study highlighted.
“We also found that as observed outside Africa, HBV viral load is a key predictor of liver disease progression and efforts should be made to increase access to viral load measurement at low cost in Africa,” she added.
Both Dr. Ndow and Prof Lemoine acknowledged that HBV is a major cause of death in Africa.
“Our previous research found that HBV is the main cause of cirrhosis and liver cancer in The Gambia, like in many African countries, and it is a leading cause of premature death,” Dr Ndow said.
“Efforts should be deployed to identify and prioritise individuals with hepatitis B who are at risk of developing cirrhosis and liver cancer” added Prof. Lemoine.
The PROLIFICA study represents a significant step towards understanding the management needs of people living with chronic hepatitis B in Africa, particularly among those considered ineligible for treatment. It provides critical insights that could shape future healthcare policies and treatment strategies.
The research conducted by MRC-G at LSHTM underscores the importance of ongoing investigation into the management of chronic hepatitis B in Africa. Future studies will be essential to validate these findings and potentially re-define treatment guidelines in low-income settings. This study was funded by the MRC UKRI and EU Commission, with support from Gilead Sciences.
Gibril Ndow is supported by the Africa Research Excellence Fund (AREF) and Wellcome Trust.
