Natural History and Hepatocellular Carcinoma Risk in Untreated Chronic Hepatitis B Patients with Indeterminate Phase (117/120). Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Huang, D. Q., Li, X. n., Le, M. H., Le, A. K., Yeo, Y. H., Trinh, H. N., Zhang, J. n., Li, J. n., Wong, C. n., Wong, C. n., Cheung, R. C., Yang, H. I., Nguyen, M. H. 2021


Many patients with chronic hepatitis B (CHB) may not conform to any of the defined phases, hence classified as indeterminate. We aimed to characterize the baseline prevalence of indeterminate patients and their natural history, phase transition and hepatocellular carcinoma (HCC) risk.This is a retrospective cohort study of 3,366 adult untreated non-cirrhotic CHB patients seen at five U.S. clinics and seven Taiwanese townships who had at least one year of serial laboratory data prior to enrollment with a mean follow-up of 12.5 years. Patients' clinical phases were determined at baseline and through serial data during follow-up, based on the AASLD 2018 Guidance.At baseline, 1,303 (38.7%) patients were in the indeterminate phase. By up to year 10 of follow-up, 686 patients (52.7%) patients remained indeterminate, while 283 (21.7%) became immune active. Compared to patients who remained inactive, patients who remained indeterminate had higher 10-year cumulative HCC incidence (4.6% vs. 0.5%, P<0.0001) and adjusted hazard ratio (HR) for HCC of 14.1 (P=0.03). Among patients who remained indeterminate, age = 45 years (adjusted HR 18.4, P=0.005) was independently associated with HCC development.Nearly 40% of patients had indeterminate CHB phase. Of these, half remained indeterminate and one-fifth transitioned to the immune active phase. HCC risk in persistently indeterminate CHB was 14 times higher than inactive CHB. Among persistently indeterminate CHB patients, age = 45 years was associated with 18 times higher risk for HCC development. Further studies are needed to evaluate the potential benefit of antiviral therapy for indeterminate patients, especially in the older subgroup.

View details for DOI 10.1016/j.cgh.2021.01.019

View details for PubMedID 33465482