Longitudinal assessment of hepatic fibrosis in responders to direct‐acting antivirals for recurrent hepatitis C after liver transplantation using noninvasive methods

Abstract

Successful eradication of recurrent hepatitis C virus (HCV) infection following liver transplantation (HCV) improves graft survival. This study aimed at evaluation of hepatic fibrosis changes among long-term responders to DAA therapy for recurrent HCV after liver transplantation using noninvasive methods. Patients with significant hepatic fibrosis (≥F2) who achieved SVR12 after treatment with DAAs for recurrent HCV were included (n = 52). Hepatic fibrosis status was assessed, noninvasively, by calculation of fibrosis-4 score (FIB-4) and Aspartate Aminotransferase Platelet Ratio Index (APRI) and by measurement of graft stiffness using FibroScan at baseline and 12 and 18 months post-treatment. Acoustic radiation force imaging (ARFI) was done for all patients 12 and 18 months post-treatment. Patients were classified into two groups based on baseline liver stiffness measurement (LSM) by FibroScan; significant fibrosis (F2; n = 28) and advanced fibrosis groups (≥F3). Over 18-month follow-up period, there was serial improvement of FIB-4, APRI, and LSM by FibroScan in both groups. Higher baseline LSM and delayed initiation of antiviral therapy were significant predictors of lack of fibrosis regression (P-value 0.01 and 0.04, respectively). Fibroindices and LSM improved over time in liver transplant recipients who responded to DAAs. Baseline LSM can predict post-treatment fibrosis regression.

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

“…The decrease in these scores must have occurred due to a reduction in serum aminotransferase levels, and the fact that there was no significant increase in the number of platelets, during or after antiviral therapy. The low increase in the number of platelets in our study was possibly due to the absence of thrombocytopenia in our patients before starting the therapy with DAAs, as was also seen in the study by Omar et al 35 . Accordingly, in a study by Hsu et al 36 in non-transplanted patients with CHC treated with DAAs, an increase in the number of platelets was observed only in patients who presented with thrombocytopenia before the treatment 36 .…”

“…These data indicate a reduction in the progression of CHC to cirrhosis and, consequently, in the number of cases requiring liver transplantation as a consequence of HCV infection. However, there are few studies evaluating fibrosis regression after treatment of CHC with DAAs in liver-transplanted patients 35 . Indeed, Omar et al found a progressive improvement in the degree of liver fibrosis, as indicated by elastography and serum scores, 12 and 18 months after the treatment of CHC with DAAs in 52 liver transplant patients 35 .…”

“…However, there are few studies evaluating fibrosis regression after treatment of CHC with DAAs in liver-transplanted patients 35 . Indeed, Omar et al found a progressive improvement in the degree of liver fibrosis, as indicated by elastography and serum scores, 12 and 18 months after the treatment of CHC with DAAs in 52 liver transplant patients 35 . The regression APRI and FIB-4 scores after treatment of CHC with DAAs, in both liver transplant and non-transplant patients, can occur by reducing serum levels of liver enzymes or by increasing the number of platelets 36 .…”

Molecular Signature Predictive of Long-Term Liver Fibrosis Progression to Inform Antifibrotic Drug Development

“…24 Sustained virologic response (SVR) to anti-HCV therapies improves surrogate indicators of fibrosis such as liver stiffness in short-term, which is followed by gradual regression of histological fibrosis. 23,25 However, SVR rate with DAA post transplantation can be as low as 50% and adverse event rates can be as high as 75% when progressed to decompensated liver disease. 26 Therefore, prediction of fibrosis progression will remain relevant in a subset of post-transplant patients with HCV infection.…”

Utility of Mac‐2 Binding Protein Glycosylation Isomer to Evaluate Graft Status After Liver Transplantation

“…However, fewer studies have evaluated noninvasive assessments of liver fibrosis in LT recipients. Liver fibrosis indices based on laboratory tests, such as APRI ( 15 ) and FIB‐4 index, ( 16‐18 ) have been reported to be useful to evaluate graft fibrosis. Yoshino et al reported that liver stiffness measurements by ARFI were more useful to predict graft fibrosis after LT than blood test–based indices that are profoundly affected by clinical factors other than the extent of liver fibrosis.…”