Efficacy and safety of direct-acting antiviral therapy in previous hard-to-treat patients with recurrent hepatitis C virus infection after liver transplantation: a real-world cohort

Bernuth, Sebastian; Grimm, Dorothee; Vollmar, Johanna; Darstein, Felix; Mittler, Jens; Heise, Michael; Hoppe‐Lotichius, Maria; Galle, Peter R.; Lang, Hauke; Zimmermann, Tim

doi:10.2147/dddt.s139837

Cited by 12 publications

(10 citation statements)

References 41 publications

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“…Some reports suggest that all patients, irrespective of their HCV genotype, should be treated immediately after LT to prevent recurrent hepatitis C and fibrosis progression in the graft [19, 20]. Our results of high tolerability of DAAs also in the peri-LT period supports continuing the DAA therapy, started while patients are on the waiting list, also in the immediate post-LT period.…”

Section: Discussionsupporting

confidence: 68%

No need to discontinue hepatitis C virus therapy at the time of liver transplantation

Skoglund¹,

Lagging²,

Castedal³

2019

PLoS ONE

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Objectives Direct antiviral agents (DAA) has dramatically improved the therapy outcome of hepatitis C-virus (HCV) infection, both on the waiting-list and post liver transplantation (LT). DAA are generally well-tolerated in patients with mild to moderate liver and kidney failure, but some DAAs are contraindicated in patients with severe dysfunction of these organs. Today there are few studies of peri-LT DAA use and treatment is commonly discontinued at the time of LT. We report here our experience of DAA therapy given continuously in the perioperative LT period in a real-life setting in Sweden. Material In total 10 patients with HCV-cirrhosis, with or without hepatocellular carcinoma, and a median age of 60.5 years (range, 52–65) were treated with DAAs on the waiting list for LT, and continued in the early postoperative period without any interruption, on the basis of not having reached a full treatment course at the time of LT. Sofosbuvir and a NS5A inhibitor with or without ribavirin, or sofosbuvir and ribavirin only, were given. The distribution of genotypes was genotype 1 and 3, in 4 and 6 patients, respectively. Six of the 10 patients had previously been treated with IFN-based therapy. Results There were no adverse events leading to premature DAA discontinuation. All recipients achieved a sustained viral response 12 weeks after end-of-treatment (SVR12). At the time of LT the median MELD-score was 16.5 (range 7–21), CTP-score 9.0 (range 5–10), creatinine 82.5 μmol/L (range 56–135, reference 60–105), bilirubin 33 μmol/L (range 16–79, reference 5–25) and PK-INR 1.5 (range 1.1–1.8). The median duration of DAA therapy was 60 days (range 18–132) pre-LT, 54 days post-LT (range 8–111 days) and in total 15.5 weeks (range 12–30 weeks). Conclusion Interferon-free DAA therapy of HCV-infection given in the immediate pre- and post-operative LT period is safe, well-tolerated and yields high SVR rates.

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Section: Discussionsupporting

confidence: 68%

No need to discontinue hepatitis C virus therapy at the time of liver transplantation

Skoglund¹,

Lagging²,

Castedal³

2019

PLoS ONE

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“…[23][24][25] For example, some recommended DAA treatment deferral (ie at least 4-6 months) following potentially curative HCC management. [26][27][28][29] Third, the DAA response among patients with HCC is relevant, particularly in relation to optimum timing of initiation. In two cohort studies conducted in the United States, the virological response to DAA therapy was impaired in HCV-related HCC patients, compared to the non-HCC population.…”

Section: Introductionmentioning

confidence: 99%

“…Second, in response to the controversy around HCC recurrence risk, the timing of DAA therapy in relation to HCC management became a point of debate . For example, some recommended DAA treatment deferral (ie at least 4‐6 months) following potentially curative HCC management . Third, the DAA response among patients with HCC is relevant, particularly in relation to optimum timing of initiation.…”

Section: Introductionmentioning

confidence: 99%

Systematic review with meta‐analysis: effectiveness of direct‐acting antiviral treatment for hepatitis C in patients with hepatocellular carcinoma

Lockart

Alavi

et al. 2019

Aliment Pharmacol Ther

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Summary Background Direct‐acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection is highly curative and tolerable. Among patients with hepatocellular carcinoma (HCC), optimal timing of DAA therapy remains unclear. Data on efficacy of DAA therapy in patients with HCC would inform this decision‐making. Aim To evaluate response to DAA therapy among patients diagnosed with HCV infection and HCC. Methods Bibliographic databases and conference abstracts were searched. Meta‐analysis was conducted to pool sustained virologic response (SVR) estimates. Results Fifty‐six studies with 5522 patients with HCV and HCC were included. Overall SVR was 88.3% (95% CI 86.1‐90.4). Twenty‐seven studies included patients with prior or present HCC (n = 3126) and patients without HCC (n = 49 138), in which SVR was 88.2% (95% CI 85.0‐91.4) and 92.4% (95% CI 91.1‐93.7) among patients with and without HCC, respectively (odds ratio: 0.54, 95% CI 0.43‐0.68, P < .001). In the subgroup analyses, higher SVR was seen in patients who received curative HCC management (SVR 90.4%, 95% CI 88.3‐92.4), or treated with sofosbuvir + NS5A inhibitor DAAs (SVR 96.9%, 95% CI 94.3‐99.4), or in patients with HCV genotype 1 infection (SVR 92.0%, 95% CI 88.1‐95.6). Conclusion Response to DAA therapy was lower in patients with HCC compared to those without HCC, regardless of cirrhosis status. Among HCC patients, there was an impact of proportion with curative HCC management on DAA therapy response.

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“…9 The previously mentioned Australian TOSCAR cohort found that a baseline MELD ≥19.5 was associated with an increased need for rescue transplantation after HCV treatment. 5 This was echoed in findings from the European ELITA cohort, which found that 95% of patients with decompensated HCV cirrhosis and a MELD greater than 20 still needed a liver transplant after treatment. This cohort also found an increased risk for needing early liver transplant and a significant risk for death before and after liver transplant.…”

Section: Safety Issues In Patients With Decompensated Cirrhosismentioning

confidence: 99%

“…Furthermore, only one‐third of patients in SOLAR‐2 and less than 5% of patients in ASTRAL‐4 had decompensated cirrhosis. The TOSCAR cohort enrolled patients with decompensated hepatitis C cirrhosis (MELD score ≥15, CTP B or C) and reported a SVR12 rate of only 70% after 24 weeks of therapy with DAC and SOF . Although the mechanistic reasons for these decreased SVR12 rates are not known, they may be related to impaired intestinal drug absorption in the setting of portal hypertension and decreased hepatic drug delivery caused by capillarization of the cirrhotic liver.…”

Section: Treatment Effectiveness In Patients With Decompensated Cirrhmentioning

confidence: 99%

CON: Patients With Decompensated Cirrhosis Listed for Liver Transplantation Should Be Treated Posttransplant

Pedersen

Tarlow

Mufti

2019

Clinical Liver Disease

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Efficacy and safety of direct-acting antiviral therapy in previous hard-to-treat patients with recurrent hepatitis C virus infection after liver transplantation: a real-world cohort

Cited by 12 publications

References 41 publications

No need to discontinue hepatitis C virus therapy at the time of liver transplantation

No need to discontinue hepatitis C virus therapy at the time of liver transplantation

Systematic review with meta‐analysis: effectiveness of direct‐acting antiviral treatment for hepatitis C in patients with hepatocellular carcinoma

CON: Patients With Decompensated Cirrhosis Listed for Liver Transplantation Should Be Treated Posttransplant

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