Hepatocellular Carcinoma Risk Between Untreated Immune Tolerant Vs. Treated Immune Active Chronic Hepatitis B Patients

The risk of hepatocellular carcinoma (HCC) between chronic hepatitis B (CHB) patients in the untreated immune tolerant (U-IT) vs. treated immune active (T-IA) phases is not clear, and most data are in Asian populations. We aim to evaluate long-term risks of cirrhosis, HCC, and overall mortality between U-IT vs. T-IA CHB patients among a national cohort of U.S. Veterans. We conducted a propensity score weighted analysis of Veterans with CHB who met criteria for U-IT or T-IA from 1/1/2010 to 12/31/2021 (with follow-up through 12/31/2024). Incidence of cirrhosis, HCC, or death were compared between U-IT and T-IA groups. A total of 591 U-IT and 555 T-IA CHB patients were identified (mean age 56.4-57.5 years, 45%-50% non-Hispanic white, 37%-40% African American, 9%-10% Asian, 25%-29% concurrent diabetes, 35%-39% with FIB-4 > 3.25). Over a median follow up of 6.4 years (IQR 3.0-10.4), incidence of HCC was significantly lower in U-IT patients vs. T-IA patients (0.28 vs. 0.54 per 100 person-years; HR 0.52, 95% CI 0.32-0.83, p = 0.007). However, the risk of cirrhosis or all-cause mortality was similar between both T-IA and U-IT CHB patients. Among a predominantly non-Asian cohort of adults with CHB, we observed that HCC risk was lower in U-IT patients compared to T-IA patients. While this contrasts with some studies in Asian countries, these data do emphasize the importance of prioritizing and ensuring timely therapy for CHB patients in the IA phase. However, routine treatment in IT patients remains controversial and more data are needed to better understand long-term outcomes.