Chronic HBV infection is associated with a wide spectrum of extrahepatic manifestations with substantial variation by demographic factors, underscoring the need for comprehensive multisystem surveillance and targeted risk stratification.
Arthralgia was the most frequent extrahepatic manifestation of chronic HBV infection, affecting 13.76% of patients.
Polyneuropathy was the second most common extrahepatic manifestation, affecting 3.27% of patients with chronic HBV infection.
Glomerulonephritis occurred in 1.26% of patients with chronic HBV infection, with demographic variation in incidence.
Aplastic anemia and cryoglobulinemia were uncommon extrahepatic manifestations, occurring in 0.12% and 0.10% of patients respectively.
Polyarteritis nodosa was the rarest extrahepatic manifestation assessed, occurring in only 0.04% of patients.
The study cohort had a mean age of 60 ± 14 years, was predominantly male (56.9%), and was racially diverse with substantial representation of Asian patients.
The study used the TriNetX Global Research Network to conduct a retrospective cohort analysis of chronic HBV patients from 2000 to 2025.
Demographic factors including age, sex, race, and ethnicity showed substantial variation in the incidence of extrahepatic manifestations across all conditions studied.
This research suggests that chronic hepatitis B virus (HBV) infection affects far more than just the liver. In a large study of over 232,000 patients from multiple countries spanning 25 years, researchers found that patients with chronic HBV infection frequently develop conditions in other organ systems, including joint pain (arthralgia, in nearly 14% of patients), nerve damage (polyneuropathy, in about 3%), and kidney inflammation (glomerulonephritis, in about 1.3%), as well as rarer conditions like blood vessel inflammation (polyarteritis nodosa), blood disorders (aplastic anemia), and immune system problems (cryoglobulinemia). The study also found that who develops these complications is not random — demographic factors matter considerably. Older patients were more likely to develop most of these conditions. Men were more prone to kidney and nerve complications, while women more frequently experienced joint pain. Certain racial and ethnic groups, including Native Hawaiian/Pacific Islander, Hispanic/Latino, American Indian/Alaska Native, and Black or African American patients, showed elevated rates for specific manifestations. These patterns suggest that factors beyond the virus itself — including genetics, healthcare access, and social determinants of health — may influence how chronic HBV affects the whole body. This research suggests that healthcare providers managing patients with chronic hepatitis B should monitor not just liver health, but also watch for signs of disease in the kidneys, joints, nerves, blood vessels, and immune system, particularly in older patients and those from higher-risk demographic groups. The findings highlight the importance of multisystem surveillance and tailoring monitoring strategies based on individual patient characteristics rather than focusing solely on liver-related outcomes.
Khan S, Subedi A, Marasini A, Shrestha A, Kulsum S, Basnet K, et al.. (2026). Clinical spectrum and burden of extrahepatic manifestations in chronic hepatitis B: A multinational study from 2000 to 2025.. Medicine. https://doi.org/10.1097/MD.0000000000050775