Group summarizes guidance for the prevention, diagnosis, evaluation, and treatment of hepatitis C virus in chronic kidney disease

Embargoed for release until 5:00 p.m. ET on Monday 11 December 2023 
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Below please find summaries of new articles that will be published in the next issue of Annals of Internal Medicine. The summaries are not intended to substitute for the full articles as a source of information. This information is under strict embargo and by taking it into possession, media representatives are committing to the terms of the embargo not only on their own behalf, but also on behalf of the organization they represent. 
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1. Group summarizes guidance for the prevention, diagnosis, evaluation, and treatment of hepatitis C virus in chronic kidney disease 

Abstract: https://www.acpjournals.org/doi/10.7326/M23-2391      

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The latest clinical practice guideline from the Kidney Disease: Improving Global Outcomes (KDIGO) organization offers guidance for the prevention, diagnosis, evaluation, and treatment of hepatitis C virus (HCV) in chronic kidney disease (CKD). The guideline is a targeted update to 2018 recommendations on the same topic and were triggered by new data on antiviral treatment in patients with advanced stages of CKD, transplant of hepatitis C virus (HCV)-infected kidneys into uninfected recipients, and evolution of the viewpoint on the role of kidney biopsy in patients with kidney diseases caused by HCV.  A synopsis of the guideline is published in Annals of Internal Medicine. 

The 2022 updated guideline includes 63 total recommendations intended to assist clinicians in care of patients with HCV infection and CKD, including patients receiving dialysis and patients with a kidney transplant. Among key changes, the guideline recommends expanding treatment of HCV 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 patients with glomerulonephritis.

The synopsis includes several visual aids to help guide decision-making. These include a table comparing the changes between the 2018 and 2022 guidelines, a figure showing direct-acting antiviral (DAA) regimens with evidence of effectiveness for various chronic kidney disease (CKD) populations, and a figure describing indications for biopsy in patients with hepatitis C virus (HCV) and severe glomerulonephritis. KDIGO will assess the currency of its recommendations to determine if they need to be updated in the next 3 years.

Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. To speak with the corresponding author, Ahmed Arslan Yousuf Awan, MD, please contact Ahmed.Awan@bcm.edu.

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2. Case shows replication-competent COVID-19 travels through bloodstream to infect various tissues throughout the body

Abstract: https://www.acpjournals.org/doi/10.7326/L23-0253   
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A case report from researchers at the National Institutes of Health (NIH) shows that replication-competent SARS-CoV-2 can traffic in blood during COVID-19 and seed tissues throughout the body. The case is published in Annals of Internal Medicine.

COVID-19 infects respiratory tissues, and in some cases, live, infectous virus has been detected in tissues outside the lungs, including the brain. Viremic spread is suspected, and detection of viral RNA in blood is frequently reported. However, recovery of replication-competent virus from blood has not been previously demonstrated.

NIH researchers studied blood drawn perimortem at a patient’s time of death to confirm viremia in a fatal COVID-19 case where viral sequence in blood and tissues match. Full-length genomic sequencing of pre- and postviral culture plasma, lung, and cardiac samples demonstrated more than 99 percent sequence similarity with multiple conserved mutations compared with a reference sequence from a critically ill patient who didn’t have detectable antibodies against the virus. The authors note that use of a permissive Vero cell line increased sensitivity of detecting SARS-CoV-2 in plasma from their patient, as did using plasma from the reference patient. According to the authors, further studies are needed to determine the implications of their findings for persons infected with SARS-CoV-2 variants, those with mild illness, persons recently vaccinated, or persons with waning immunity after natural infection or vaccination.

Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. To speak with the corresponding author, Andrew Platt, MD, PhD, please contact Maria Maslennikov at maria.maslennikov@nih.gov or Yvonne Hylton at yvonne.hylton@nih.gov.

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3. Model predicts sex-specific risk for atherosclerotic cardiovascular disease using routine laboratory tests

Abstract: https://www.acpjournals.org/doi/10.7326/M23-1345     
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The CANHEART (Cardiovascular Health in Ambulatory Care Research Team) Lab Models uses routine lab tests to predict risk for sex-specific atherosclerotic cardiovascular disease (ASCVD) with similar accuracy to more complex models, such as the pooled cohort equations (PCEs). These findings suggest that ASCVD can be accurately predicted without clinical risk factors, which may greatly simplify risk prediction in routine clinical practice. The study is published in Annals of Internal Medicine.

Current risk models are underused in clinical practice because they are cumbersome, requiring physicians to collect risk factor information from medical history, physical measurements, and laboratory tests and then input these factors into risk calculators. A model that uses only laboratory tests and does not rely on clinical variables or physician input may provide a significant advantage over traditional models.

Researchers from the University of Toronto sought to develop and validate sex-specific prediction models for ASCVD using age and routine laboratory tests and compare their performance with that of the PCEs, which require more information and greater physician input. They used an internal validation cohort of more than 3 million men and women to test the CANHEART lab models, measuring serum total cholesterol, high density lipoprotein cholesterol, triglycerides, hemoglobin, mean corpuscular volume, platelets, leukocytes, estimated glomerular filtration rate, and blood glucose – all standard lab tests. The researchers found that the models were well calibrated, with relative differences of less than 1 percent between mean predicted and observed risk for both sexes. The authors say future studies are needed to determine whether automating these models in daily practice improves prescribing of preventive treatments according to clinical practice guidelines.

Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. To speak with the corresponding author, Dennis T. Ko, MD, MSc, please contact Samantha Sexton at samantha.sexton@sunnybrook.ca.

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4. For large colonic adenomas, en bloc resection significantly reduced the risk for local recurrence

Abstract: https://www.acpjournals.org/doi/10.7326/M23-1812  
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A randomized controlled trial of more than 300 people with large benign colonic lesions has found that the use of endoscopic submucosal dissection (ESD) for removal was associated with a significantly lower 6-month recurrence rate compared with endoscopic mucosal resection (EMR). However, ESD was associated with more adverse events. The findings are published in Annals of Internal Medicine.

Endoscopic resection of adenomas prevents colorectal cancer, but the optimal technique for larger lesions is controversial. Piecemeal EMR has a low adverse event rate but a variable recurrence rate necessitating early follow-up. ESD can reduce recurrence but may increase adverse events.

Researchers from Service d’Hepato-Gastro-Enterologie, Limoges, France conducted a participant-masked, parallel-group, superiority, randomized controlled trial of 360 patients with large benign colonic lesions. Participants were randomly assigned to undergo ESD or EMR. The authors found that ESD was associated with a 0.6 percent rate of recurrence, while EMR was associated with a 5.1 percent rate of recurrence. Adverse events occurred for 35.6 percent of ESD procedures compared with 24.5 percent of EMR procedures.  R0 resection was achieved in 93.8% of cases in the ESD allowing no early follow up colonoscopy in this situation whereas piece-meal resection need 6 and 18 months follow-up colonoscopy according to guidelines.

According to the authors, patients and physicians should be aware of these study results not only to know when to choose endoscopic resection instead of surgery but also to choose the endoscopic resection strategy that best fits the patient according to the lesion, the acceptance of follow-up colonoscopy, and the available expertise at the center.

  
Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. To speak with the corresponding author, Jeremie Jacques, MD, PhD, (jeremiejacques@gmail.com) please contact Maite Belacel at maite.belacel@chu-limoges.fr.

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5. Physicians debate the best management strategy for a patient with heart failure with preserved ejection fraction

‘Beyond the Guidelines’ features are based on the Department of Medicine Grand Rounds at Beth Israel Deaconess Medical Center

Abstract: https://www.acpjournals.org/doi/10.7326/M23-2384 

URL goes live when the embargo lifts

In a new Annals ‘Beyond the Guideline’s feature, a cardiologist and a geriatrician discuss their approach to the diagnosis and management of heart failure with preserved left ventricular ejection fraction and how they would apply guidelines to an individual patient. All ‘Beyond the Guidelines’ features are based on the Department of Medicine Grand Rounds at Beth Israel Deaconess Medical Center (BIDMC) in Boston and include print, video, and educational components published in Annals of Internal Medicine. 

The proportion of patients with new-onset heart failure that have preserved (HFpEF) rather than reduced (HFrEF) left ventricular ejection fraction has been increasing over recent decades. In fact, HFpEF now outweighs HFrEF as the predominant heart failure subtype and likely remains underdiagnosed in the community. This increased prevalence is due in part to an aging population and a rise in risk factors for HFpEF, including obesity and associated cardiometabolic disease. Whereas the diagnosis of HFrEF is relatively straightforward, the diagnosis of HFpEF is often more challenging because there can be other causes for symptoms including dyspnea and fatigue.

BIDMC Grand Rounds discussants, Jennifer E. Ho, MD, a cardiologist, Associate Professor of Medicine at Harvard Medical School, and a member of the Division of Cardiology at BIDMC, and Ariela R. Orkaby, MD, MPH, a geriatrician, Assistant Professor of Medicine at Harvard Medical School, and a member of the New England Geriatric Research, Education, and Clinical Center (GRECC) at VA Boston and Division of Aging at Brigham and Women’s Hospital, recently debated the case of Ms. B, a 77-year-old woman with dyspnea, a history of coronary artery bypass surgery, and suspected HFpEF.

Both Dr. Ho and Dr. Orkaby agree that Ms. B has HFpEF. Dr. Orkaby agrees with Dr. Ho in many

aspects of caring for patients with HFpEF. However, Dr. Ho favors an “opt-out” medication strategy and also stresses the importance of a healthy lifestyle, including exercise and calorie restriction. Dr. Orkaby favors an “opt-in” strategy when selecting and sequencing medications. Dr. Ho feels that CPET testing could help to determine the relative contribution of COPD to her symptoms. Dr. Ho recommends SGLT2i, ARNi, and MRA treatment in an “opt-out” strategy, along with diuretics. Dr. Orkaby recommends beginning with a discussion about goals of care, which would include a focus on physical function. Dr. Orkaby agrees with an SGLT2i, would deprescribe the b -blocker, and recommends weight loss, multimodal physical rehabilitation, and a palliative care consultation with a focus on symptom management.

A complete list of ‘Beyond the Guidelines’ topics is available at www.annals.org/grandrounds.

Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. For an interview with the discussants, please contact Kendra McKinnon at kmckinn1@bidmc.harvard.edu.