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The use of highly effective and well-tolerated direct antiviral agents against hepatitis C virus (HCV) in the setting of liver transplant has many potential implications.
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With current oral combinations, treatment of patients before and after liver transplant results in sustained viral response rates greater than 95% except in the subset of patients with severely advanced liver disease with portal hypertension.
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The decision to treat before or after liver transplant should take into consideration
The New Era of Hepatitis C: Therapy in Liver Transplant Recipients
Section snippets
Key points
When to treat hepatitis C virus in patients who need liver transplant
If initiated when there is less severe fibrosis, the response rate to DAAs is superior to that of patients treated at a more advanced stage of the disease, particularly at the stage of decompensated cirrhosis.30, 31, 32 In recent reports, favorable response rates have been achieved, even in those with more advanced cirrhosis, including Child-Turcotte-Pugh (CTP) class B and C, with surprisingly few severe adverse effects30, 31, 32 (Table 1).
The decision to treat patients who are listed for
Treatment of Patients with Cirrhosis
The treatment of patients with cirrhosis on the waiting list for transplant is the same as for those not listed. Details of the response rates on this patient population are outside the scope of this review. For patients with genotypes 1 and 4, the combination of sofosbuvir with ledipasvir, daclatasvir, or velpatasvir has high response rates and is well tolerated.30, 31, 32, 43 Other options are the combination of elbasvir and grazoprevir; the combination of paritaprevir, ritonavir, ombitasvir,
Sofosbuvir and Ribavirin
The combinations of sofosbuvir and ribavirin for a period of 24 weeks was first used in patients with genotypes 1 and 4, with fibrosis varying from none/minimal to cirrhosis and an overall response rate of 70% at 12 weeks.57 The efficacy of this regimen was later proved to be inferior to the combination of sofosbuvir with a second DAA and currently the combination of sofosbuvir and ribavirin is limited to the treatment of patients with HCV genotype 2.
Sofosbuvir and Ledipasvir
The use of sofosbuvir and the NS5A inhibitor
Fibrosing cholestatic hepatitis
Fibrosing cholestatic hepatitis (FCH), characterized by rapid progression of portal fibrosis and cholestasis following transplant, is estimated to occur in 2% to 10% of patients. It is suggested that FCH results from the effects of direct viral toxicity in the context of immunosuppression.62 The prognosis of FCH is poor (50%–90% mortality in 2 years) and, given the nature of the disease, retransplant of the affected patients is controversial.
The early attempts to treat FCH with pegylated
Resistance-associated variants
When properly chosen and properly taken, the current, more potent, DAAs rarely fail to achieve eradication of the HCV virus. Nonadherence, especially during the early phase of treatment, is associated with the emergency of RAVs.63 Although there are some circumstances in which failure to achieve SVR is not associated with the virus itself, the emergence of RAVs is the main reason for failure to eradicate the virus. It is estimated that 53% to 91% of patients with virologic relapse harbor HCV
Summary
The advent of the DAAs has revolutionized transplant hepatology with an expected shift away from HCV as the main reason for LT in Europe and the United States in the near future.
With the exception of patients with genotype 2, who can be successfully treated with sofosbuvir and ribavirin, the combination of 2 DAAs with or without ribavirin is the mainstay in the treatment of patients with HCV posttransplant.
Sofosbuvir in combination with ledipasvir, daclatasvir, or simeprevir with or without
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Liver Transpl
Cited by (7)
Delisting and clinical outcomes of liver transplant candidates after hepatitis C virus eradication: A long-term single-center experience
2021, Clinics and Research in Hepatology and GastroenterologyCitation Excerpt :However, we identified that patients with MELD scores >18 did not have liver function improvements sufficient to warrant delisting. This result corresponds to algorithms, in which authors recommend antiviral treatment for patients with decompensated cirrhosis and MELD scores <20 during the pre-LT period because they are more likely to attain significant improvements and can be removed from the waiting list after HCV eradication [22,23]. For this reason, European Association for the Study of the Liver guidelines (2018) also recommend initiating treatment for patients with MELD score ≤18 before LT [24].
Improved Outcomes in HCV Patients Following Liver Transplantation During the Era of Direct-Acting Antiviral Agents
2018, Clinical Gastroenterology and HepatologyRevolution in the diagnosis and management of hepatitis C virusinfection in current era
2022, World Journal of HepatologyCirculating MicroRNAs: Dynamic Markers of Liver Transplant Injury
2022, TransplantationRecent advances in liver transplantation with HCV seropositive donors
2019, F1000ResearchChanges in practice and perception of hepatitis C and liver transplantation: Results of a national survey
2018, Transplant Infectious Disease
Disclosures: Dr M. Berenguer discloses that Ciberehd is partially funded by the Instituto de Salud Carlos III (ISCIII). Dr E.C. Little has nothing to disclose.