Martina Gambato
Credit: EPAteam
Sustained virological response (SVR) was associated with improvements in hepatic function, liver fibrosis, and post-liver transplantation survival in a retrospective cohort study of HCV-infected liver transplant recipients who received direct-acting antiviral (DAA) treatment after liver transplantation.
“The safety and efficacy of DAAs after liver transplantation are widely accepted, but only a few studies have described the long-term impact of viral eradication on liver function and survival after liver transplantation,” wrote investigators.1 “We aimed to evaluate the long-term impact of viral eradication on fibrosis progression and patient survival after liver transplantation in HCV-infected recipients, reporting the efficacy and safety data of DAAs in this population.”
The World Health Organization recommends DAAs for all adults, adolescents, and children down to 3 years of age with chronic HCV because of its effectiveness and short treatment duration. Globally, around 62% of individuals with HCV had been treated with DAAs by the end of 2019.2
To assess long-term impacts of DAAs on liver function and post-liver transplantation survival, a team of investigators led by Martina Gambato, of the Department of Oncological and Gastroenterological Surgical Sciences of the University of Padua, conducted a retrospective cohort study using data from consecutive liver transplant recipients with HCV who received DAA treatment after liver transplant between May 2014 and January 2019 and who were included in the NAVIGATORE web-based platform or in the DAAs’ compassionate use program in Italy. The liver fibrosis stage at the baseline was F4 in 41% of patients (n = 56), F3 in 23% (n = 31), F2 in 22% (n = 30), and F0–1 in 14% (n = 19).1
Patients underwent clinical and laboratory assessments including liver function tests, blood cell count, ALT, AST, serum creatinine, and HCV-RNA levels every 4 weeks during the treatment period and at 3, 6, 12, 24, and 36 months after the end of treatment. Treatment efficacy was measured as SVR12, defined by investigators as undetectable HCV-RNA by a quantitative RT-PCR with a limit of detection of 12 IU/mL 12 weeks after the end of treatment. Investigators compared groups using a t-test or Mann–Whitney test for continuous variables, chi-square or Fisher tests for categorical variables, and Wilcoxon test for paired variables.1
Upon analysis, the SVR12 rate after the first DAA regimen was 78.7%. The overall SVR12 rate including responders to second treatment was 96%. Among liver transplant recipients who achieved SVR, the platelet count increased significantly at the end of treatment (P < 0.001) and then remained stable at SVR12 (P = 0.06), at SVR24 (P = 0.74), and at year 1, 2, and 3 after the EoT (P = 0.46, P = 0.18, and P = 0.37, respectively). The same result was observed in patients with liver cirrhosis.1
ALT levels decreased significantly at the end of treatment (P < 0.001) and from the end of treatment to SVR12 (P = 0.001) and then remained stable at SVR24 (P = 0.42) and at year 1, 2, and 3 after the EoT (P = 0.84, P = 0.65, and P = 0.23). In cirrhotic patients, ALT levels decreased significantly at the end of treatment (P < 0.001) and continued to decrease from the end of treatment to SVR12 (P = 0.008), remaining stable thereafter (P = 0.5, P = 0.57, P = 0.05, and P = 0.57).1
Among patients who achieved SVR, 77 had paired liver stiffness measurements [LSM] at the baseline and between the first and the fourth year after the end of treatment. Fibrosis improvement was observed in 31% of patients. Overall, liver stiffness decreased significantly from a median value of 11.9 kPa (Interquartile Range [IQR] 8–16.4) to a median value of 7.9 kPa (IQR 5.9–14.2) (P = 0.003).1
The only two factors that were found to be associated with lower survival in the univariate and multivariate analyses were platelet count < 50,000/mm3 (P = 0.04) and higher creatinine levels at the baseline (P = 0.03).1
“Our findings confirmed that viral eradication with DAAs after [liver transplantation] improves liver function and patient survival after a long-term follow-up, even in cirrhotic patients. In addition, our study showed that [liver transplantation] recipients with portal hypertension before treatment were less likely to benefit from DAAs and experienced lower survival rates,” concluded investigators.1
References:
1. Gambato M, Manuli C, Lynch EN et al. Long-Term Impact of Direct-Acting Antivirals on Liver Fibrosis and Survival in HCV-Infected Liver Transplant Recipients. Viruses. 2023; 15(8):1702. https://doi.org/10.3390/v15081702
2. World Health Organization. Hepatitis C. Newsroom. Accessed September 1, 2023. https://www.who.int/news-room/fact-sheets/detail/hepatitis-c
