Chronic hepatitis B (CHB) imposes substantial economic and social burdens globally. The management of CHB involves intricate monitoring and adherence challenges, particularly in regions like China, where a high prevalence of CHB intersects with health care resource limitations. This study explores the potential of ChatGPT-3.5, an emerging artificial intelligence (AI) assistant, to address these complexities. With notable capabilities in medical education and practice, ChatGPT-3.5's role is examined in managing CHB, particularly in regions with distinct health care landscapes. This study aimed to uncover insights into ChatGPT-3.5's potential and limitations in delivering personalized medical consultation assistance for CHB patients across diverse linguistic contexts. Questions sourced from published guidelines, online CHB communities, and search engines in English and Chinese were refined, translated, and compiled into 96 inquiries. Subsequently, these questions were presented to both ChatGPT-3.5 and ChatGPT-4.0 in independent dialogues. The responses were then evaluated by senior physicians, focusing on informativeness, emotional management, consistency across repeated inquiries, and cautionary statements regarding medical advice. Additionally, a true-or-false questionnaire was employed to further discern the variance in information accuracy for closed questions between ChatGPT-3.5 and ChatGPT-4.0. Over half of the responses (228/370, 61.6%) from ChatGPT-3.5 were considered comprehensive. In contrast, ChatGPT-4.0 exhibited a higher percentage at 74.5% (172/222; P<.001). Notably, superior performance was evident in English, particularly in terms of informativeness and consistency across repeated queries. However, deficiencies were identified in emotional management guidance, with only 3.2% (6/186) in ChatGPT-3.5 and 8.1% (15/154) in ChatGPT-4.0 (P=.04). ChatGPT-3.5 included a disclaimer in 10.8% (24/222) of responses, while ChatGPT-4.0 included a disclaimer in 13.1% (29/222) of responses (P=.46). When responding to true-or-false questions, ChatGPT-4.0 achieved an accuracy rate of 93.3% (168/180), significantly surpassing ChatGPT-3.5's accuracy rate of 65.0% (117/180) (P<.001). In this study, ChatGPT demonstrated basic capabilities as a medical consultation assistant for CHB management. The choice of working language for ChatGPT-3.5 was considered a potential factor influencing its performance, particularly in the use of terminology and colloquial language, and this potentially affects its applicability within specific target populations. However, as an updated model, ChatGPT-4.0 exhibits improved information processing capabilities, overcoming the language impact on information accuracy. This suggests that the implications of model advancement on applications need to be considered when selecting large language models as medical consultation assistants. Given that both models performed inadequately in emotional guidance management, this study highlights the importance of providing specific language training and emotional management strategies when deploying ChatGPT for medical purposes. Furthermore, the tendency of these models to use disclaimers in conversations should be further investigated to understand the impact on patients' experiences in practical applications.