Optimization of hepatological clinical guidelines interpretation by large language models: a retrieval augmented generation-based framework
Open accessAbstract
Large language models (LLMs) can potentially transform healthcare, particularly in providing the right information to the right provider at the right time in the hospital workflow. This study investigates the integration of LLMs into healthcare, specifically focusing on improving clinical decision support systems (CDSSs) through accurate interpretation of medical guidelines for chronic Hepatitis C Virus infection management. Utilizing OpenAI’s GPT-4 Turbo model, we developed a customized LLM framework that incorporates retrieval augmented generation (RAG) and prompt engineering. Our framework involved guideline conversion into the best-structured format that can be efficiently processed by LLMs to provide the most accurate output. An ablation study was conducted to evaluate the impact of different formatting and learning strategies on the LLM’s answer generation accuracy. The baseline GPT-4 Turbo model’s performance was compared against five experimental setups with increasing levels of complexity: inclusion of in-context guidelines, guideline reformatting, and implementation of few-shot learning. Our primary outcome was the qualitative assessment of accuracy based on expert review, while secondary outcomes included the quantitative measurement of similarity of LLM-generated responses to expert-provided answers using text-similarity scores. The results showed a significant improvement in accuracy from 43 to 99% ( p < 0.001), when guidelines were provided as context in a coherent corpus of text and non-text sources were converted into text. In addition, few-shot learning did not seem to improve overall accuracy. The study highlights that structured guideline reformatting and advanced prompt engineering (data quality vs. data quantity) can enhance the efficacy of LLM integrations to CDSSs for guideline delivery.
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Some studies defined hallucinations as nonfactual information, while one study added input-conflicting and contextual-conflicting types.
“Some studies defined hallucinations as nonfactual information, while one study added 2 other types of hallucinations: input-conflicting (content deviating from user-provided input) and contextual-conflicting (content conflicting with previously generated information).27,41”
From Improving large language model applications in biomedicine with retrieval-augmented generation: a systematic review, meta-analysis, and clinical development guidelines (2025) · cites this paper as [27]
The Methods (Primary outcome; page unavailable) define three categories—fact-conflicting, input-conflicting, and contextual-conflicting hallucinations—and the Results (Output accuracy analysis; page unavailable) use those categories. Our copy does not spell out the cited sentence’s definitions of input- and contextual-conflicting content. It also says the categories follow Zhang et al., rather than claiming this study introduced them. (LLM, conf=0.82)
Experimental — accuracy not yet measuredA preliminary study found that GPT-4 Turbo had only a 16% accuracy rate in extracting table data.
“a preliminary study found that GPT-4 Turbo had only a 16% accuracy rate in extracting table data.27”
Only 3 studies in the review explicitly mentioned extracting text from tables or figures during the pre-retrieval process.
“Only 3 studies in our review explicitly mentioned extracting text from tables or figures during the pre-retrieval process.25,27,44”
Kresevic et al. (2024) showed significant performance improvements from incorporating RAG to interpret Hepatitis C guidelines, with their customized framework increasing accuracy from 43% to 99%.
“Furthermore, Kresevic et al. (2024) showed significant performance improvements from incorporating RAG to interpret Hepatitis C guidelines, with their customized framework increasing accuracy from 43% to 99%.”
From Grounding Large Language Models in Clinical Evidence: A Retrieval-Augmented Generation System for Querying UK NICE Clinical Guidelines (2025) · cites this paper as Kresevic et al. (2024)
The results confirm the findings of smaller-scale studies showing clear benefits of implementing RAG architectures over baseline LLMs.
“The results confirm the findings of smaller-scale studies, such as those by Ferber et al. (2024) and Kresevic et al. (2024), showing clear benefits of implementing RAG architectures over baseline LLMs.”
From Grounding Large Language Models in Clinical Evidence: A Retrieval-Augmented Generation System for Querying UK NICE Clinical Guidelines (2025) · cites this paper as Kresevic et al. (2024)
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Summary of ChatGPT-Related research and perspective towards the future of large language models
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“The results confirm the findings of smaller-scale studies, such as those by Ferber et al. (2024) and Kresevic et al. (2024), showing clear benefits of implementing RAG architectures over baseline LLMs.”
- Authors
- Kresevic, S., Giuffrè, M., Ajcevic, M., Accardo, A., Crocè, L. S., & Shung, D. L.
- Affiliations
- University of Trieste (IT)
- Yale University (US)
- Corresponding author
- Kresevic, Simone
- Giuffrè, Mauro
- Venue
- npj Digital Medicine
- Published
- 2024-04-23
- Volume
- 7
- Issue
- 1
- Pages
- 102-102
- ISSN
- 2398-6352 (ISSN-L)
- PMC
- PMC11039454
- OpenAlex
- W4395050972
- Cited by
- 207
- References
- 5
- Citations by year
- 2026: 70 · 2025: 109 · 2024: 28
- FWCI
- 19.35
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- npj Digital Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ArTS Archivio della ricerca di Trieste (University of Trieste https://www.units.it/) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (UL1TR001863)
- National Institute of Diabetes and Digestive and Kidney Diseases (K23DK125718)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Health Informatics › Artificial Intelligence in Healthcare and Education
- Physical Sciences › Computer Science › Artificial Intelligence › Machine Learning in Healthcare
- Physical Sciences › Computer Science › Artificial Intelligence › Topic Modeling
- Keywords
- large language models, retrieval-augmented generation, clinical decision support systems, chronic hepatitis C, prompt engineering, GPT-4 Turbo, few-shot learning, text similarity
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