Burden of Chronic hepatitis B virus infection in adults without cirrhosis

Published estimates of the number of persons living with hepatitis B virus (HBV) infection in the United States range from 580,000 to 2.4 million. In the National Health and Nutrition Examination Survey (NHANES), 0.2% of persons aged 6 years and older, an estimated 660,000 persons, had HBV infection, and 49.8% of them were aware of it; non-US-born persons accounted for 73.6% of those infected. Modeling studies estimated 1.8 million HBV-positive individuals in the United States in 2020 (prevalence 0.55%) and 1.7 million in the United States and Puerto Rico (prevalence 0.50%). In the 2020 model, approximately 334,800 infections (18%) were diagnosed, and 90,500 of 534,100 individuals eligible for treatment (just under 17%) were treated; 35,000 of the 36,400 new chronic infections in 2020 (96%) were among immigrants.

During 2023, 17,650 newly reported cases of chronic hepatitis B were reported to CDC by 44 states and the District of Columbia (6.1 cases per 100,000 population); the rate among non-Hispanic Asian and Pacific Islander persons was 18.9 cases per 100,000 population. Worldwide, 240 million people (2.9% of the population) were living with chronic HBV infection in 2024, of whom 27% had been diagnosed and 4.3% were on treatment, and 0.9 million people were newly infected that year.

Approximately 15%–25% of people with chronic HBV infection develop chronic liver disease, including cirrhosis, liver failure, or liver cancer. Reported annual cirrhosis incidence ranges from 2% to 7% in tertiary care cohorts and was 0.7% in a study of 1506 asymptomatic carriers; persons with cirrhosis progress to decompensated cirrhosis at an estimated 3% annually, with 5-year survival of 84% in compensated and 14%–28% in decompensated cirrhosis. In a cohort followed for a mean of 11.4 years, hepatocellular carcinoma (HCC) incidence ranged from 108 per 100 000 person-years at a baseline HBV DNA level below 300 copies/mL to 1152 per 100 000 person-years at 1 million copies/mL or greater. Among 2,496 patients with non-cirrhotic chronic hepatitis B, incidences of cirrhosis and HCC were 3.99 and 0.43 per 100 person-years. Among 1,644 patients treated with entecavir or tenofovir, the 10- and 15-year cumulative incidences of HCC were 10.9% and 13.2%.

In the United States, 1,769 hepatitis B-related deaths were reported during 2023 (age-adjusted rate 0.44 deaths per 100,000 population). In a cohort of 4389 patients with chronic hepatitis B followed for a mean of 5.38 years, 492 (11%) died, at an average age of 59.8 years, “14 years younger than the general U.S. population”, and hepatitis B was reported on the death certificates of 19% of decedents. Annual U.S. liver-related deaths are projected to increase by 25% from 7900 in 2019 to 9900 in 2030, and annual HCC incidence by 31% from 6500 to 8500 cases. Worldwide, an estimated 1.1 million HBV-related deaths occurred in 2024, an increase of 17% from 2015.

In a meta-analysis of 19 studies comprising 10,311 patients (74% of studies in the Western Pacific Region), predicted mean utility scores were 0.842 for non-cirrhotic chronic HBV infection, 0.820 for compensated cirrhosis, 0.722 for decompensated cirrhosis, and 0.749 for HCC. A meta-analysis of 31 studies estimated the prevalence of depressive symptoms at 19% and of anxiety at 30% among individuals with hepatitis B. In a systematic review of 23 studies of HBV-related stigma, up to 20% of respondents believed they may be denied healthcare and up to 30% that they may experience workplace discrimination.

In U.S. Commercial, Medicare, and Medicaid claims from 2004 to 2015 (33,904 chronic hepatitis B cases), mean annual all-cause healthcare costs among commercially insured patients were $142,870 with decompensated cirrhosis, $124,123 with HCC, and $171,851 with liver transplantation, compared with $18,619 with compensated liver disease (98% non-cirrhotic); patients with compensated liver disease had three times the annual healthcare cost of matched controls without chronic hepatitis B. In the U.S. National Inpatient Sample, total costs of hospitalizations of patients with chronic hepatitis B were $603.82 million in 2016 and $809.01 million in 2019. A U.S. model projected $44,822 million in cumulative direct medical costs associated with HBV between 2020 and 2050.