Sofosbuvir and simeprevir combination therapy in the setting of liver transplantation and hemodialysis

Perumpail, Ryan B.; Wong, Robert J.; Ha, Le Dung; Pham, Edward A.; Wang, U.; Luong, Hoang Van; Kumari, Rita; Daugherty, Tami; Higgins, Julian P T; Younossi, Zobair M.; Kim, Woojin; Glenn, Jeffrey S.; Ahmed, Aijaz

doi:10.1111/tid.12348

Cited by 38 publications

(44 citation statements)

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“…This study included traditionally difficult to treat patients, with 43% being previously treated nonresponders and 52% being either transplant recipients or having decompensated cirrhosis. The SVR rate in this study compares favorably to those reported in other studies, which vary widely from 67% to 100%16, 17, 18, 19, 20, 21, 22, 23 (Table 2). Several aspects of these other studies may have contributed to reduced SVR rates, including the use of reduced‐dose SOF18, 19, 20 and the use of regimens with less potential to achieve SVR, such as SOF/RBV and SOF/pegylated interferon/RBV 16, 17…”

Section: Discussionsupporting

confidence: 83%

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: Discussionsupporting

confidence: 83%

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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“…After screening and reviewing abstracts, 71 studies were excluded according to exclusion criteria. Seven studies were relevant, of which one case report and two case series were excluded (27)(28)(29). Finally, only four clinical studies were included for meta-analysis (Figure 1).…”

Section: Resultsmentioning

confidence: 99%

Efficacy and Safety of Sofosbuvir with Simeprevir in Hepatitis C Infected Patients with Severe Chronic Kidney Disease: A Systematic Review and Meta-Analysis

et al. 2016

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Background & Aims:Conventional treatment (interferon or ribavirin) for Hepatitis C viral (HCV) infection in patients with severe chronic kidney disease (CKD) has limitations of high dropout and less response rate. Directly acting antivirals raise hopes for HCV treatment in these patients. This meta-analysis was performed to evaluate the evidence for efficacy and safety of sofosbuvir and simeprevir, with or without ribavirin, in HCV-infected patients with severe CKD. Methods: Data was collected from Medline database, clinical-trial registry sites, and conference proceedings. This meta-analysis screened 78 studies. Quality of studies was assessed by New-Castle Ottawa scale. Heterogeneity and publication bias was checked by chi-square Q test and Eggers' test, respectively. Summary estimate of SVR12 and dropout rate was calculated at 95% confidence interval (CI). Results: Seven relevant clinical studies were identified. Two case-series and one case-report were excluded; only four studies were eligible for analysis. Three studies were cohort and one was retrospective-cohort in nature. Data was analyzed for 56 subjects. 33/56 subjects had cirrhosis. 39/56 subjects were on hemodialysis. 37/56 subjects were male. 30/56 subjects were treatment-naive. Pooled estimate of SVR12 was found 0.897 (CI 95%=0.957-0.772; p<0.01) and dropout estimate was 0.040 (CI 95%=0.011-0.137; p<0.01). Only one subject discontinued the treatment due to worsening Renal function regardless of ribavirin. Conclusion: This study concluded that combination of sofosbuvir and simeprevir, with or without ribavirin, was significantly effective and safe in HCV patients with severe CKD. For conclusive results, more data is required as this study involved only limited number of subjects.

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“…SVR12 rates were not different between 12 or 24 wk of treatment, with or without RBV, and comparing naive patients to experienced (95% vs 91%) [87,88] . In this small study, the regimen SOF plus SMV with or without RBV was well tolerated; the most common side effects were headache, fatigue, and nausea, and only four (2%) patients discontinued treatment due to these events.…”

Section: Second-generation Pismentioning

confidence: 99%

“…In post-liver transplant patients with HCV infection, co-administration of SMV with cyclosporine resulted in significantly elevated SMV levels, so it is not recommended [87] . SMV can be safely administered with tacrolimus or sirolimus.…”

Section: Second-generation Pismentioning

confidence: 99%

“…SMV is well tolerated, and adverse reactions in patients receiving SMV in combination with PEG-IFN-α [86] . Coadministration of SMV with inhibitors of cytochrome P450 3A (CYP3A) is not recommended.In post-liver transplant patients with HCV infection, co-administration of SMV with cyclosporine resulted in significantly elevated SMV levels, so it is not recommended [87] . SMV can be safely administered with tacrolimus or sirolimus.…”

mentioning

confidence: 99%

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Chronic hepatitis C: This and the new era of treatment

Bertino

Ardiri

Proiti

et al. 2016

WJH

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Over the last years it has started a real revolution in the treatment of chronic hepatitis C. This occurred for the availability of direct-acting antiviral agents that allow to reach sustained virologic response in approximately 90% of cases. In the near future further progress will be achieved with the use of pan-genotypic drugs with high efficacy but without side effects. Core tip: This review analyzes the current therapies for chronic hepatitis C and the future challenges of the research. So it tries to give an update on the research of hepatitis C virus (HCV) infection, providing a critical view of the emerging therapies and their impact on the future management of HCV infection. Since novel TOPIC HIGHLIGHT Chronic hepatitis C: This and the new era of treatment2016 Hepatitis C Virus: Global view treatments for HCV infection are highly efficacious but costly, priority should be given to patients with advanced hepatic fibrosis, which is a disease that cannot be deferred. INTRODUCTIONThe hepatitis C virus (HCV), identified in the 70s but cloned in 1989, is a single-stranded RNA virus belonging to the family Flaviviridae.HCV is the main cause of progressive liver diseases and a public health problem worldwide. It is estimated that approximately 150-180 million people in the world are living with chronic hepatitis [1,2] , 350 million of whom die each year from liver damage associated with the infection [3] . About 80% of people infected with HCV develop chronic hepatitis, of which 20%-40% will develop liver cirrhosis or hepatocellular carcinoma (HCC) 20-30 years after infection.As a consequence, chronic HCV infection is the major reason of liver transplantation in developed countries [4][5][6][7] . According to the Global Burden Disease Study in Europe, the death rate for viral hepatitis is significantly higher than that for human immunodeficiency virus (HIV) and acquired immune deficiency syndrome; in particular in 2010, the number of deaths from viral hepatitis have been ten times bigger than that attributed to HIV. It is reasonable to think that this difference is due to the lack of effective therapies for HCV until a few years ago [8] .HCV is also one of the main causes of death [9] . The virus causes both liver damage and extra-hepatic manifestations, many of these syndromes are associated with the ability of HCV to replicate in peripheral blood mononuclear cells (PBMCs); an example is the mixed cryoglobulinemia, which is by far the most common extrahepatic disease closely connected with the infection.Recently it was shown that antiviral treatment is associated with improved renal and cardiovascular outcomes in patients with cryoglobulinemia [4,6,10,11] . Newly approved oral anti-HCV drugs are very safe and effective, but unfortunately their cost will force to choose a priority of treatment. The intent should therefore be to identify and treat patients with a higher risk of morbidity and mortality due to HCV.The availability of these new oral treatments can definitely heal patients and ...

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Sofosbuvir and simeprevir combination therapy in the setting of liver transplantation and hemodialysis

Cited by 38 publications

References 4 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

Efficacy and Safety of Sofosbuvir with Simeprevir in Hepatitis C Infected Patients with Severe Chronic Kidney Disease: A Systematic Review and Meta-Analysis

Chronic hepatitis C: This and the new era of treatment

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