Initiating direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) during hospitalization, particularly among persons who inject drugs, presents an opportunity to capitalize on the novel advancements in HCV therapy over the past decade. The OPPORTUNI-C (Midgard et al.; Table 1) trial was a randomized trial conducted across seven clinical departments in Norway evaluating completion of DAA therapy within six months in patients who started therapy inpatient. The intervention significantly increased treatment initiation and completion rates compared to the control group, which followed standard outpatient referral practices. However, sustained virologic response (SVR) rates did not differ between groups at the final data lock, primarily due to higher loss to follow-up in the intervention arm rather than treatment failure. Despite lower absolute SVR rates, the early initiation of DAAs likely led to improved cure rates, reinforcing the importance of inpatient treatment as a critical intervention point. Logistical constraints such as delayed HCV RNA test results and short hospital stays limited the intervention’s reach, with 7% of eligible patients not starting therapy while hospitalized. Additionally, 40% of RNA-positive patients were discharged before enrollment, raising concerns about engagement strategies beyond hospitalization. Structural barriers within the fragmented U.S. healthcare system (e.g., Medicaid coverage gaps, prior authorization restrictions, and pricing discrepancies between inpatient and outpatient medications) limit the replicability of this model domestically. More realistic solutions in the US may include patient outreach programs, partnerships with needle-exchange programs, and offering drop-in visits (or telehealth) to patients. [1], [2]
A 2023 implementation study evaluated the feasibility and effectiveness of integrating direct-acting antiviral (DAA) initiation during hospitalization as part of inpatient HCV treatment coordination for patients who inject drugs (PWID). The study involved 28 hospitalized PWID who tested positive for HCV. The program used e-consults for care coordination, and of the 28 patients, 82% were linked to care, with 73% starting DAAs and 52% completing the treatment. Among inpatient initiators, 73% achieved a sustained virologic response (SVR), while 71% of non-inpatient initiators were linked to care, 53% started treatment, and 36% achieved the outcome. The median age of participants was 33 years, with 82% being white and 61% uninsured. The median length of hospital stay was 23 days, and 93% of patients received medication for opioid use disorder (MOUD). Identified challenges included barriers to accessing cellphones, which led to some patients being lost to follow-up. However, the results indicated that inpatient DAA initiation combined with telehealth follow-up was a feasible and effective strategy to improve retention in HCV care for PWID. The authors emphasized that future efforts should address barriers to inpatient DAA initiation and expand the model to other populations with similar needs. [3]
A 2023 retrospective review assessed the outcomes of patients who initiated HCV treatment with DAAs while hospitalized. A total of 17 patients started DAA treatment during hospitalization. Sixteen of the patients (94%) were treated with glecaprevir-pibrentasvir for 8 weeks, and one patient (6%) received sofosbuvir-velpatasvir for 12 weeks. Of these, 16 patients (94%) reported injection drug use, and 12 (71%) had unstable housing; the majority of patients had medicare insurance. Notably, 12 patients (71%) completed their treatment, with nine of these patients achieving SVR12. Findings also revealed that despite incomplete treatment, two out five patients who did not finish their regimen still attained SVR2. Based on these findings, it was concluded that initiating HCV treatment during hospitalization provides a valuable opportunity for curing the infection in vulnerable populations with significant barriers to accessing outpatient care. However, further evaluation is needed to optimize strategies for inpatient HCV treatment initiation. Of note, only the abstract of the study was available for scrutiny, limiting a comprehensive analysis of these findings. [4]
A 2023 educational review published in the American Society of Hematology (ASH) Education Program discusses the recognition and management of hemophagocytic lymphohistiocytosis (HLH) in hospitalized patients, emphasizing the diagnostic complexities and therapeutic considerations associated with this hyperinflammatory syndrome. HLH is described as a severe immune dysregulation disorder that may arise in the presence of genetic abnormalities, hematologic malignancies, chronic inflammatory states, or infections. The review highlights the challenges of distinguishing HLH from other systemic inflammatory disorders, given its overlapping clinical features, including fever, cytopenias, neurological symptoms, and elevated inflammatory markers such as ferritin and soluble CD25. Through an in-depth analysis of available diagnostic criteria—including the HLH-2004 guidelines and the HScore—the review underscores the importance of early recognition to improve patient outcomes. [5]
Emerging biomarkers such as C-X-C motif chemokine ligand 9 (CXCL9) and interleukin-18 (IL-18) are also discussed as potential tools to differentiate HLH from sepsis and other mimicking conditions. The review further explores therapeutic decision-making, balancing the urgency of immune suppression with the need to identify and treat HLH triggers. Various treatment modalities are examined, including the HLH-94 protocol, which integrates etoposide and corticosteroids, as well as newer targeted therapies such as emapalumab, a monoclonal interferon-gamma (IFN-γ inhibitor), and Janus kinase (JAK) inhibitors like ruxolitinib. A case study of a 45-year-old male with Epstein-Barr virus (EBV)-associated HLH demonstrates the disease's diagnostic and management challenges, illustrating the necessity of prompt viral load assessment, immunosuppressive therapy initiation, and continuous vigilance for treatment response. The review also considers HLH subtypes, including malignancy-associated HLH (M-HLH) and macrophage activation syndrome (MAS), advocating for tailored therapeutic approaches based on disease triggers and underlying immune dysregulation. Through comprehensive evaluation and individualized treatment strategies, the review emphasizes improving diagnostic accuracy and optimizing patient outcomes in this life-threatening condition. Overall, the benefits of initiating HCV treatment inpatients versus outpatient is not discussed; however, it may be assumed that the review is advocating for inpatient treatment since the discussion is related to the inpatient setting. [5]