A 2-Step Strategy Combining FIB-4 With Transient Elastography and Ultrasound Predicted Liver Cancer After HCV Cure

Abstract

INTRODUCTION: Despite the direct-acting antiviral therapy has dramatically decreased the likelihood of having liver-related complications and extrahepatic outcomes, the risk of developing hepatocellular carcinoma (HCC) is not totally eliminated after sustained virological response (SVR). We aimed to develop an easy-to-apply strategy to be adopted in clinical practice for accurately classifying the HCC risk in hepatitis C virus patients after SVR. METHODS: Prospective and multicenter study enrolling hepatitis C virus patients with advanced fibrosis (transient elastography [TE] > 10 kPa) or cirrhosis by ultrasound showing SVR. They were followed up until HCC, liver transplantation, death, or until October 2020, which occurred first, with a minimum follow-up period of 6 months after SVR (follow-up: 49 [interquartile range 28–59] months). RESULTS: Patients with cirrhosis by ultrasound represented 58% (611/1,054) of the overall cohort. During the study, HCC occurrence was 5.3% (56/1,054). Multivariate analyses revealed that Fibrosis-4 (FIB-4) > 3.25 (hazard ratio [HR] 2.26 [1.08–4.73]; P = 0.030), TE (HR 1.02 [1.00–1.04]; P = 0.045) and cirrhosis by ultrasound (HR 3.15 [1.36–7.27]; P = 0.007) predicted HCC occurrence. Baseline HCC screening criteria (TE > 10 kPa or cirrhosis) identified patients at higher risk of HCC occurrence in presence of FIB-4 > 3.25 (8.8%; 44/498) vs FIB-4 < 3.25 (2.4%; 12/506), while those with only FIB > 3.25 had no HCC (0%; 0/50) (logRank 22.129; P = 0.0001). A combination of baseline FIB-4 > 3.25 and HCC screening criteria had an annual incidence >1.5 cases per 100 person-years, while the rest of the groups remained <1 case. Patients who maintained post-treatment FIB-4 > 3.25 and HCC screening criteria remained at the highest risk of HCC occurrence (13.7% [21/153] vs 4.9% [9/184]; logRank 7.396, P = 0.007). DISCUSSION: We demonstrated that a two-step strategy combining FIB-4, TE, and ultrasound could help stratify HCC incidence risk after SVR.

Update on the role of elastography in liver disease

“…A recent multicenter prospective study, including more than 1000 patients who achieved SVR after treatment with DAAs, has reported that patients with VCTE values >10 kPa or with cirrhosis assessed by US before the treatment had a higher risk for HCC if the FIB-4 was >3.25 with respect to patients with FIB-4 < 3.25. 54 The rate of HCC occurrence was 8.8% in the former group and 2.4% in the latter group. Of note, patients who maintained FIB-4 >3.25 and VCTE values >10 kPa after SVR had the highest risk of HCC occurrence (13.7%).…”

Hepatocellular Carcinoma in Chronic Viral Hepatitis: Where Do We Stand?

“…Therefore, there is a strong need for methods to assess individual patient risk. In a recent prospective multicenter study including 1054 patients with advanced fibrosis (stiffness >10 kPa) or cirrhosis (58% of the total) with a minimum of a six-month follow-up after DAAs, Ampuero et al investigated the predictors of HCC [ 126 ]. HCC was observed in 56 patients (5.3%) after therapy and was independently predicted by Fibrosis-4 (FIB-4) > 3.25 (hazard ratio [HR] 2.26 [1.08–4.73]; p = 0.030), liver stiffness by transient elastography (HR 1.02 [1.00–1.04]; p = 0.045) and baseline cirrhosis by ultrasound (HR 3.15 [1.36–7.27]; p = 0.007).…”

“…More interestingly, a combination of baseline FIB-4 > 3.25 and HCC screening criteria (cirrhosis or liver stiffness > 10 kPa) had an annual incidence > 1.5 cases per 100 person-years, while the patients lacking these predictors remained at <1 case. Patients who maintained post-treatment FIB-4 > 3.25 and were either cirrhotics or had baseline liver stiffness >10 kPa remained at the highest risk of HCC occurrence (13.7% [21/153] vs. 4.9% [9/184]; logRank 7.396, p = 0.007) [ 126 ].…”

Who needs follow-up after cure HCV infection?

“…Pretratamiento, el mayor riesgo de CHC fue identificado por la combinación de FIB-4 >3,25 con ET >10 kPa o cirrosis por ecografía. El riesgo de CHC se triplicaba si mantenían estos criterios a los 6 meses tras fin del tratamiento 35 . Es llamativo que no desarrolló CHC ninguno de los pacientes que pretratamiento tenían 10-13,5 KPa, sin cirrosis en ecografía y FIB-4 <3,25; lo que sugiere que en ellos se podría evitar el cribado, por muy bajo riesgo de CHC.…”

“…Alonso observó el mayor descenso de la RHM y del FIB-4 en el primer año, aunque a los 3 años siguieron descendiendo (probablemente continuó la regresión hepática). Es destacable que el estudio de Ampuero y de Ioannou obtuvieron resultados similares [35][36][37] .…”