A Complex Case of Hemophagocytic Lymphohistiocytosis Secondary to Untreated Hepatitis C: Diagnostic Challenges
Bibliographic record
Abstract
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome caused by uncontrolled activation of cytotoxic T cells and macrophages, leading to cytokine storm and organ failure. Secondary HLH is the acquired form that is commonly triggered by underlying malignancies, autoimmune diseases, or infections. While Epstein-Barr virus (EBV) is a common infectious trigger for HLH, hepatitis C virus (HCV) is rarely reported in the literature. Herein, we present the case of a patient with HLH with multiple possible infectious triggers that was ultimately attributed to HCV. A 61-year-old male with a history of untreated HCV was admitted with concerns for septic shock. Infectious workup was largely negative throughout his hospitalization. Lumbar puncture was concerning for a fungal meningitis, but fungal workup was negative except for a positive Blastomyces dermatitidis antibody. In addition, acid-fast bacilli culture eventually grew Mycobacterium porcinum (M. porcinum). He was treated with broad-spectrum antibiotics and anti-fungals but continued to fever. He met five of eight criteria per HLH-2004 protocol and was initiated on HLH-directed therapy with immediate resolution of his fevers. A Karius test did not identify pathogenic levels of Blastomyces dermatitidis or M. porcinum in the serum, and the causative trigger was determined to be his untreated HCV. This case highlights the importance of early recognition and treatment of HLH in a patient with fever of unknown origin. It brings attention to HCV as a highly unusual trigger of HLH. It also illustrates the difficulty in addressing the underlying source of secondary HLH when a broad infectious workup yields several rare but possible pathogens.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.005 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.002 | 0.002 |
| Scholarly communication | 0.002 | 0.003 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.005 | 0.004 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".