Impact of Sustained Virologic Response with Direct‐Acting Antiviral Treatment on Mortality in Patients with Advanced Liver Disease

Backus, Lisa I.; Belperio, Pamela S.; Shahoumian, Troy A.; Molé, L

doi:10.1002/hep.29408

Cited by 191 publications

(197 citation statements)

References 28 publications

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“…However, when stratified by eras, the higher waitlist mortality was noted only in the pre‐DAA era and not in the post‐DAA era. This observation is likely attributable to the advent of DAA therapies and corresponds to the relationship between increased success of SVR with DAA therapy and the correlation between SVR and improved mortality for chronic HCV patients …”

Section: Discussionmentioning

confidence: 99%

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Improved liver transplant waitlist mortality and lower risk of disease progression among chronic hepatitis C patients awaiting liver transplantation after the introduction of direct‐acting antiviral therapies in the United States

Young

Liu

Bhuket

et al. 2018

Journal of Viral Hepatitis

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Summary Direct‐acting antiviral (DAA) therapies for chronic hepatitis C virus (HCV) infection achieve high cure rates, reducing HCV‐related disease progression to cirrhosis and hepatocellular carcinoma. We aim to evaluate the impact of DAAs on US liver transplant (LT) waitlist outcomes. We retrospectively evaluated US adults (age ≥18) with and without chronic HCV listed for LT before and after the widespread use of sofosbuvir, allowing a 6‐month period after approval (Era 1: 1/1/2002‐5/31/2014 vs Era 2: 6/1/2014‐12/31/2016) using the United Network for Organ Sharing registry. Overall, LT waitlist survival and likelihood of receiving LT were evaluated with multivariate Cox regression models. From 2002 to 2016, 158 045 patients were listed for LT. While the number of patients listed for HCV has been decreasing since 2012, the proportion of HCV patients with concurrent HCC is increasing by 3.33% per year (R2: 0.99, P < 0.001 by simple linear regression). While there was no difference in likelihood of LT between HCV and non‐HCV patients, those listed in Era 2 had lower likelihood of LT (HR: 0.91, P < 0.001), more pronounced in the HCV cohort (HR: 0.83, P < 0.001) compared to the non‐HCV cohort (HR: 0.93, P < 0.001). Compared to non‐HCV patients, higher waitlist mortality was seen in HCV patients in Era 1 (HR: 1.08, P < 0.001) but not in Era 2 (HR: 1.02, P = 0.75). Since the introduction of DAAs for HCV treatment, number of patients with HCV listed for LT has declined. In the post‐DAA era, HCV patients on the LT waitlist had improved waitlist mortality.

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Section: Discussionmentioning

confidence: 99%

“…Achieving SVR is associated with decreased HCV‐related liver failure, HCC, mortality and need for LT and has been demonstrated with both interferon therapy and DAAs . Studies have also shown that SVR can also lead to regression of fibrosis .…”

Section: Introductionmentioning

confidence: 99%

Improved liver transplant waitlist mortality and lower risk of disease progression among chronic hepatitis C patients awaiting liver transplantation after the introduction of direct‐acting antiviral therapies in the United States

Young

Liu

Bhuket

et al. 2018

Journal of Viral Hepatitis

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“…With the caveat that follow-up time for DAA-treated patients is still limited, evidence is accumulating that SVR may be associated with fibrosis regression (25), improvement in portal pressures (26, 27), improvement in extrahepatic manifestations of HCV (28, 29), and reduced risk of mortality (30, 31). However, enthusiasm for DAAs was tempered after a series of publications reported potentially higher than expected rates of HCC following DAA treatment.…”

Section: Daa Treatment and De Novo Hccmentioning

confidence: 99%

The Impact of Direct-acting Antiviral Therapy for Hepatitis C on Hepatocellular Carcinoma Risk

Ioannou

2018

Curr Hepatology Rep

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Purpose of review Direct-acting antiviral agents (DAAs) eradicate hepatitis C virus (HCV) infection in the majority of patients. We critically evaluated the impact of DAAs on hepatocellular carcinoma (HCC) risk, a major complication of HCV infection. Recent findings Large cohort studies show that patients who achieve sustained virologic response (SVR) with DAAs have a significantly lower risk of developing de novo HCC than patients who fail treatment or remain untreated. Furthermore, reduction in HCC risk is similar whether SVR is achieved with DAAs or interferon (IFN). However, DAA-induced SVR does not eliminate HCC risk entirely. Therefore, patients with pre-existing cirrhosis require ongoing surveillance even after SVR is achieved. Early, descriptive, uncontrolled reports suggested that DAAs may increase the risk of recurrent HCC. While studying HCC recurrence presents major methodologic challenges, larger studies containing appropriate comparison control groups largely refuted these concerns. Summary Recent studies provide evidence that DAA-induced SVR reduces HCC risk.

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“…1–6 For the last two decades, chronic HCV infection was the leading indication for liver transplant (LT) in the United States. Treatment of HCV infection prior to 2014 consisted primarily of interferon- and ribavirin-based treatment regimens, which had limited efficacy, were associated with debilitating side effects, and, generally, were contraindicated in patients with decompensated cirrhosis or, in the case of ribavirin, advanced chronic kidney disease (CKD).…”

Section: Introductionmentioning

confidence: 99%

The impact of direct-acting antiviral agents on liver and kidney transplant costs and outcomes

Axelrod

Schnitzler

Alhamad

et al. 2018

American Journal of Transplantation

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Direct-acting antiviral medications (DAAs) have revolutionized care for hepatitis C positive (HCV+) liver (LT) and kidney (KT) transplant recipients. Scientific Registry of Transplant Recipients registry data were integrated with national pharmaceutical claims (2007-2016) to identify HCV treatments before January 2014 (pre-DAA) and after (post-DAA), stratified by donor (D) and recipient (R) serostatus and payer. Pre-DAA, 18% of HCV+ LT recipients were treated within 3 years and without differences by donor serostatus or payer. Post-DAA, only 6% of D-/R+ recipients, 19.8% of D+/R+ recipients with public insurance, and 11.3% with private insurance were treated within 3 years (P < .0001). LT recipients treated for HCV pre-DAA experienced higher rates of graft loss (adjusted hazard ratio [aHR] 1.85 , P < .0001) and death (aHR 1.68 , P < .0001). Post-DAA, HCV treatment was not associated with death (aHR 0.67 , P = .25) or graft failure (aHR 0.64 , P = .20) in D+R+ LT recipients. Treatment increased in D+R+ KT recipients (5.5% pre-DAA vs 12.9% post-DAA), but did not differ by payer status. DAAs reduced the risk of death after D+/R+ KT by 57% ( 0.43 , P = .04) and graft loss by 46% ( 0.54 , P = .08). HCV treatment with DAAs appears to improve HCV+ LT and KT outcomes; however, access to these medications appears limited in both LT and KT recipients.

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Impact of Sustained Virologic Response with Direct‐Acting Antiviral Treatment on Mortality in Patients with Advanced Liver Disease

Abstract: Those achieving SVR after direct-acting antiviral treatment had significantly lower all-cause mortality and lower incident HCC rates than those who did not achieve SVR. (Hepatology 2017).

Cited by 191 publications

References 28 publications

Improved liver transplant waitlist mortality and lower risk of disease progression among chronic hepatitis C patients awaiting liver transplantation after the introduction of direct‐acting antiviral therapies in the United States

Improved liver transplant waitlist mortality and lower risk of disease progression among chronic hepatitis C patients awaiting liver transplantation after the introduction of direct‐acting antiviral therapies in the United States

The Impact of Direct-acting Antiviral Therapy for Hepatitis C on Hepatocellular Carcinoma Risk

The impact of direct-acting antiviral agents on liver and kidney transplant costs and outcomes

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