METHODS: The KDIGO Work Group (WG) updated the guideline, which included reviewing and grading new evidence that was identified and summarized. As in the previous guideline, the WG used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to appraise evidence and rate the strength of recommendations and used expert judgment to develop recommendations. New evidence led to updating of recommendations in the chapters on treatment of hepatitis C virus (HCV) infection in patients with CKD (Chapter 2), management of HCV infection before and after kidney transplant (Chapter 4), and diagnosis and management of kidney disease associated with HCV infection (Chapter 5). Recommendations in chapters on detection and evaluation of hepatitis C in CKD (Chapter 1) and prevention of HCV transmission in hemodialysis units (Chapter 3) were not updated because of an absence of significant new evidence.
RECOMMENDATIONS: The 2022 updated guideline includes 43 graded recommendations and 20 ungraded recommendations, 7 of which are new or modified on the basis of the most recent evidence and consensus among the WG members. The updated guidelines recommend expanding treatment of hepatitis C with sofosbuvir-based regimens to patients with CKD glomerular filtration rate categories G4 and G5, including those receiving dialysis; expanding the donor pool for kidney transplant recipients by accepting HCV-positive kidneys regardless of the recipient's HCV status; and initiating direct-acting antiviral treatment of HCV-infected patients with clinical evidence of glomerulonephritis without requiring kidney biopsy. The update also addresses the use of immunosuppressive regimens in such patients.
SOURCES OF DATA: Recent published literature.
AREAS OF AGREEMENT: Corticosteroids and immunomodulators that antagonize the interleukin-6 (IL-6) receptor have been shown to play a critical role in modulating inflammation and improving clinical outcomes in hospitalized patients. Inhaled budesonide reduces the time to recovery in older patients with mild-to-moderate COVID-19 managed in the community.
AREAS OF CONTROVERSY: The clinical benefit of remdesivir remains controversial with conflicting evidence from different trials. Remdesivir led to a reduction in time to clinical recovery in the ACTT-1 trial. However, the World Health Organization SOLIDARITY and DISCOVERY trial did not find a significant benefit on 28-day mortality and clinical recovery.
GROWING POINTS: Other treatments currently being investigated include antidiabetic drug empagliflozin, antimalarial drug artesunate, tyrosine kinase inhibitor imatinib, immunomodulatory drug infliximab, antiviral drug favipiravir, antiparasitic drug ivermectin and antidepressant drug fluvoxamine.
AREAS TIMELY FOR DEVELOPING RESEARCH: The timing of therapeutic interventions based on postulated mechanisms of action and the selection of clinically meaningful primary end points remain important considerations in the design and implementation of COVID-19 therapeutic trials.
METHODS: A pilot study was conducted in four primary healthcare (PHC) centers in Malaysia. The model's key features included on-site HCV ribonucleic acid (RNA) testing using a shared GeneXpert® system; noninvasive biomarkers for cirrhosis diagnosis; and extended care to PWID referred from nearby PHC centers and outreach programs. The feasibility assessment focused on three aspects of the model: demand (i.e., uptake of HCV RNA testing and treatment), implementation (i.e., achievement of each step in the HCV care cascade), and practicality (i.e., ability to identify PWID with HCV and expedite treatment initiation despite resource constraints).
RESULTS: A total of 199 anti-HCV-positive PWID were recruited. They demonstrated high demand for HCV care, with a 100% uptake of HCV RNA testing and 97.4% uptake of direct-acting antiviral treatment. The rates of HCV RNA positivity (78.4%) and sustained virologic response (92.2%) were comparable to standard practice, indicating the successful implementation of the model. The model was also practical, as it covered non-opioid-substitution-therapy-receiving individuals and enabled same-day treatment in 71.1% of the participants.
CONCLUSIONS: The modified same-day test-and-treat model is feasible in improving HCV care for rural PWID. The study finding suggests its potential for wider adoption in HCV care for hard-to-reach populations.