Two meta-analyses conducted by researchers at the Institut Pasteur show that the risk of serious complications linked to chronic hepatitis B is underestimated in some patients. This research directly contributed to the updating of World Health Organization (WHO) guidelines, enabling more people to access antiviral treatment at an earlier stage.
Researchers from the Institut Pasteur have published two meta-analyses in The Lancet Gastroenterology & Hepatology that challenge the criteria for access to treatment for chronic hepatitis B and are helping to shape global health guidelines.
A silent disease with serious consequences
Chronic hepatitis B affects around 300 million people worldwide. It can progress silently over many years towards severe complications: cirrhosis, liver cancer, and even premature death. Until recently, WHO recommended that access to antiviral treatment for patients without cirrhosis should be limited to individuals with a high viral load – that is, a large amount of virus in the blood (exceeding 20,000 international units per milliliter (IU/mL)). Below this threshold, most patients were generally not eligible for treatment.
An underestimated risk at lower viral loads
Yusuke Shimakawa and his team conducted two meta-analyses by combining data from numerous existing studies. Their findings are unequivocal: although the risk of complications does indeed increase with viral load, it is nonetheless significant well below the threshold previously used. Moreover, elevated levels of liver enzymes, including ALT (markers of liver inflammation), constitute a significant risk factor. In other words, some at-risk patients have until now been excluded from the WHO treatment criteria.
The second meta-analysis confirms the effectiveness of antiviral treatments in patients with a high viral load or abnormal ALT levels. Uncertainties remain for the mildest cases, an area that the researchers say warrants further investigation, particularly in sub-Saharan Africa, where the disease is widespread.
Findings that are shifting the global landscape
This research directly informed the revision of the WHO guidelines published in 2024: in people without cirrhosis or significant fibrosis, the viral load threshold for initiating treatment was lowered from 20,000 to 2,000 IU/mL, when associated with elevated ALT levels. In practical terms, this means that a greater number of patients will be able to benefit from antiviral treatment at an earlier stage, thereby reducing the risk of serious complications. This represents a major step forward in the global ambition to eliminate viral hepatitis as a public health threat by 2030.
Sources:
- Natural history of chronic hepatitis B in untreated adults without cirrhosis according to baseline hepatitis B virus DNA and alanine aminotransferase concentrations: a systematic review and meta-analysis. Daniela Yucuma, Arthur Rakover, Zakary Ismail Warsop et al., The Lancet Gastroenterology & Hepatology, May 2026.
- Efficacy of antiviral therapy in adults with chronic hepatitis B according to baseline hepatitis B virus DNA and alanine aminotransferase concentrations: a systematic review and meta-analysis. Yu Ri Im, Si Emma Chen, Rukmini Jagdish et al., The Lancet Gastroenterology & Hepatology, May 2026.
