Direct‐acting antiviral agents for liver transplant recipients with recurrent genotype 1 hepatitis C virus infection: Systematic review and meta‐analysis

Abstract

Background Comprehensive evaluation of safety and efficacy of different combinations of direct‐acting antivirals (DAAs) in liver transplant recipients with genotype 1 (GT1) hepatitis C virus (HCV) recurrence remains limited. Therefore, we performed this systematic review and meta‐analysis in order to evaluate the clinical outcome of DAA treatment in liver transplant patients with HCV GT1 recurrence. Methods Studies were included if they contained information of 12 weeks sustained virologic response (SVR12) after DAA treatment completion as well as treatment related complications for liver transplant recipients with GT1 HCV recurrence. Results We identified 16 studies comprising 885 patients. The overall pooled estimate proportion of SVR12 was 93% (95% confidence interval (CI): 0.89, 0.96), with moderate heterogeneity observed (τ2 = 0.01, P < 0.01, I2=75%). High tolerability was observed in liver transplant recipients reflected by serious adverse events (sAEs) with pooled estimate proportion of 4% (95% CI: 0.01, 0.07; τ2 = 0.02, P < 0.01, I2 = 81%). For subgroup analysis, a total of five different DAA regimens were applied for treating these patients. Sofosbuvir/Ledipasvir (SOF/LDV) led the highest pooled estimate SVR12 proportion, followed by Paritaprevir/Ritonavir/Ombitasivir/Dasabuvir (PrOD), Daclatasvir (DCV)/Simeprevir (SMV) ± Ribavirin (RBV), and SOF/SMV ± RBV, Asunaprevir (ASV)/DCV. There was a tendency for favoring a higher pooled SVR12 proportion in patients with METAVIR Stage F0‐F2 of 97% (95% CI: 0.93, 0.99) compared to 85% (95% CI: 0.79, 0.90) for stage F3‐F4 (P < 0.01). There was no significant difference between LT recipients treated with or without RBV (P = 0.23). Conclusions Direct‐acting antiviral treatment is highly effective and well‐tolerated in liver transplant recipients with recurrent GT1 HCV infection.

A Case Report of Alloimmune Hepatitis after Direct-acting Antiviral Treatment in a Liver Transplant Patient

“… 3 – 5 Several studies have demonstrated that DAA treatments are well tolerated in liver transplant patients and are successful at achieving sustained virologic response in more than 95% of patients. 6 Serious adverse events can occur, however, including rashes, cytopenia, allograft rejection, severe anemia, and mortality, but these were only reported in 4% of cases 7 and thus our case is an unusual presentation following DAA therapy. The exact pathogenesis is not fully understood but believed to share similar histological and clinical findings with classical AIH.…”

A real-life study on the impact of direct-acting antivirals in the treatment of chronic hepatitis C in liver transplant recipients at two university centers in Northeastern Brazil

“…reported in a systematic review involving 885 transplanted patients, all of the cases associated with genotype 1, with higher SVR rates (p < 0.01) in patients with METAVIR F0-F2 (SVR = 97%, 95% CI: 0.93-0.99), when compared to patients with F3-F4 (SVR = 85%, 95% CI: 0.79-0.90) 32 .…”

“…It is possible that the lower response rate was due to the predominance of genotype 3 two thirds of the cases), and more patients with advanced fibrosis (F4) being included. These two factors, genotype 3 and advanced fibrosis/cirrhosis are predictive of lower SVR in both transplanted and non-transplanted patients 31,32 .…”

Consensus on management of hepatitis C virus infection in resource-limited Ukraine and Commonwealth of Independent States regions

“…In patients with cirrhosis, the rates of SVR ranged from 94% to 100% in the four treatment groups[30]. Several other clinical and real-world studies and meta-analyses have also reported the efficacy of this regimen in treating HCV GT1-infected patients, including: (1) Both treatment naïve and treatment-experienced patients[31-49]; (2) Patients with compensated cirrhosis or advanced liver disease[31,36,38,40,44-46,48,50-52]; and (3) Liver transplantation cases (the transplantation cases studied included treatment-naïve as well as treatment-experienced and those with cirrhosis and HCC prior to transplantation)[50,53-59]. The presence of fibrosis, cirrhosis, or HCC has been found to lower the SVR rates with sofosbuvir and ledipasvir combination in HCV GT1-infected patients in a few studies[56,58-62].…”