Treatment With Ledipasvir–Sofosbuvir for 12 or 24 Weeks in Kidney Transplant Recipients With Chronic Hepatitis C Virus Genotype 1 or 4 Infection

Colombo, Massimo; Aghemo, Alessio; Hong, Liu; Zhang, Jie; Dvory‐Sobol, Hadas; Hyland, Robert H.; Yun, Chohee; Massetto, Benedetta; Brainard, Diana M.; McHutchison, John G.; Bourlière, Marc; Peck‐Radosavljevic, Markus; Manns, Michael P.; Pol, Stanislas

doi:10.7326/m16-1205

Cited by 169 publications

(151 citation statements)

References 30 publications

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“…It is worth noting that worsening renal function has been reported in subjects receiving SOF‐based regimens who have moderate renal impairment16 or have undergone kidney transplant 24. Because no control was available for these studies, it is difficult to attribute the worsening renal function to SOF exposure versus natural progression of disease.…”

Section: Discussionmentioning

confidence: 99%

Sofosbuvir‐based regimens for the treatment of chronic hepatitis C in severe renal dysfunction

Cox-North

Hawkins

Rossiter

et al. 2017

Hepatology Communications

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Sofosbuvir (SOF) is a nonstructural 5B polymerase inhibitor with activity in all hepatitis C virus (HCV) genotypes and is the backbone of many anti‐HCV drug regimens. SOF is converted into inactive metabolites that undergo renal excretion. Patients with an estimated glomerular filtration rate (eGFR) < 30 mL/minute/1.73 m2 may experience increased drug exposure and thus potential toxicities along with decreased efficacy due to dose reduction or drug discontinuation. This is a single‐center study evaluating safety and effectiveness of SOF‐based regimens in patients with severe renal dysfunction, defined as eGFR <30 mL/minute/1.73 m2, including those receiving concurrent hemodialysis. Data were collected from patients with HCV and severe renal dysfunction who started full‐dose (400 mg) SOF‐based antiviral therapy ± ribavirin between April 2014 and February 2016. Medical records were reviewed for demographics, medical history, laboratory, radiologic imaging, echocardiography, transplant status, and liver pathologic findings. Twenty‐nine patients were identified; 12 had cirrhosis and 4 of those had decompensated cirrhosis. Fourteen patients had undergone transplantation of liver and/or kidney and were on calcineurin inhibitors, with 42% requiring dose increases or decreases while on therapy. All patients attained viral suppression on treatment, and 97% had a sustained viral response at 12 weeks posttreatment. There were no early treatment discontinuations. One death occurred posttreatment from a non‐ST elevation myocardial infarction in a patient with a history of coronary artery disease and ischemic cardiomyopathy. Conclusion: SOF‐based regimens appear safe in a broad range of patients with severe renal dysfunction, including those with decompensated cirrhosis and liver transplant. To confirm these retrospective findings, prospective studies that include SOF and SOF metabolite measurements coupled with prospective serial monitoring of electrocardiograms and echocardiograms are needed. (Hepatology Communications 2017;1:248‐255)

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Section: Discussionmentioning

confidence: 99%

Sofosbuvir‐based regimens for the treatment of chronic hepatitis C in severe renal dysfunction

Cox-North

Hawkins

Rossiter

et al. 2017

Hepatology Communications

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“…It is important to note that the KDPI was derived from graft outcomes determined from a cohort of patients transplanted between 1995 and 2005, a time when HCV infection was not easily or commonly treated after transplant due to the risk that interferon-α could lead to rejection [9]. Therefore, it is quite possible that the overall quality of kidneys from HCV-infected donors is being underestimated now that we can readily cure HCV infection after kidney transplant with direct-acting antiviral therapies that do not compromise graft function [10-13]. A recent analysis by Scalea et al [14] even suggests that HCV-infected KT recipients accepting HCV-infected kidneys may have higher rates of graft survival than those accepting uninfected donor kidneys, possibly mediated by their decreased time on dialysis prior to transplant.…”

Section: Discussionmentioning

confidence: 99%

Effect of the Opioid Crisis on the Donor Pool for Kidney Transplantation: An Analysis of National Kidney Deceased Donor Trends from 2010–2016

Chute

Sise

2018

Am J Nephrol

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Background: The opioid crisis has led to a dramatic increase in the number of drug overdose deaths in the United States. Little is known about the effect of the opioid crisis on the kidney transplant donor pool, particularly on hepatitis C virus (HCV)-infected donors. Methods: This is a retrospective analysis of the data from the Organ Procurement and Transplantation Network from 2010 to 2016. We determined the changes in characteristics of kidney transplant donors and evaluated which changes may be directly related to the opioid crisis. Results: Between 2010 and 2016, we found a 26% increase in overall donors, including a 277% increase in the number of donors who died from drug overdose. Nineteen percent of donors who died of drug overdose had HCV infection. Donors who die from drug overdose and donors with HCV infection are younger, less likely to have diabetes or hypertension, and have favorable kidney donor profile index scores compared to average donors. Despite these favorable characteristics, HCV-infected donors appear to be notably underutilized, with substantially lower kidneys per donor being transplanted compared to HCV uninfected donors. Conclusion: The opioid crisis in the United States has substantially altered the kidney donor pool. Strategies to increase utilization of all potentially viable kidneys for transplant are needed, particularly in this era of new, highly effective, direct-acting antiviral therapy for HCV infection.

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“…A RCT in HCV-1 and 4 infected patients with long-term stable KT demonstrated the safety and efficacy (100% success rate) of a 12 week ribavirin-free regimen based on sofosbuvir/ledipasvir [120]. The favorable outcomes of IFN-free therapy for HCV in KT patients have been confirmed by a real-life study where the safety of treatment in terms of prevention of graft rejection was optimal in patients who started therapy at least 3 months after transplantation [121].…”

Section: Sofosbuvir-free Combination Regimens Based On Protease Inhibmentioning

confidence: 99%

Current and future challenges in HCV: insights from an Italian experts panel

et al. 2017

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Treatment With Ledipasvir–Sofosbuvir for 12 or 24 Weeks in Kidney Transplant Recipients With Chronic Hepatitis C Virus Genotype 1 or 4 Infection

Abstract: Gilead Sciences.

Cited by 169 publications

References 30 publications

Sofosbuvir‐based regimens for the treatment of chronic hepatitis C in severe renal dysfunction

Sofosbuvir‐based regimens for the treatment of chronic hepatitis C in severe renal dysfunction

Effect of the Opioid Crisis on the Donor Pool for Kidney Transplantation: An Analysis of National Kidney Deceased Donor Trends from 2010–2016

Current and future challenges in HCV: insights from an Italian experts panel

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