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      • Long-Term Course of Cirrhosis Regression: Lessons from Patients with HCV Cirrhosis Following Successful Sofosbuvir-Based Treatment

        ( Ira Jacobson ),( Andrew J. Muir ),( Eric Lawitz ),( Edward Gane ),( Brian Conway ),( Peter J. Ruane ),( Ziad Younes ),( Frances Chen ),( Marianne Camargo ),( Anand P. Chokkalingam ),( C. Stephen Dje 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

        Aims: In patients with HCV cirrhosis, a sustained virologic response (SVR) is associated with improved clinical outcomes; however, the temporal course of changes in fibrosis is poorly understood. Our aim was to evaluate changes in noninvasive tests of fibrosis (NITs) in this setting to gain insights into the natural history of cirrhosis regression following removal of the causative exposure. Methods: We studied patients with HCV cirrhosis who achieved SVR with sofosbuvir (SOF)-based regimens (in a trial or clinical practice) in an ongoing, prospective cirrhosis registry (NCT02292706). Patients underwent routine clinical and laboratory assessments, including semi-annual Child-Pugh-Turcotte (CPT) scoring and measurement of the Enhanced Liver Fibrosis (ELF) test, as well as annual liver stiffness measurement by transient elastography (LS by TE). Changes in fibrosis were estimated based on ELF response (defined as ≥0.5 unit reduction), and shifts in estimated fibrosis categories based on ELF (F3, ELF 9.8-11.3; F4, ELF >11.3) and LS by TE (F3, 9.6-12.5 kPa; F4, >12.5 kPa). Logistic regression was used to identify predictors of fibrosis improvement as defined by NITs. Results: 1,574 subjects with HCV cirrhosis (32% female, 39% BMI ≥30 kg/㎡, 7% CPT class B/C) were included in this study; median interval between SVR and registry enrollment was 38 weeks (IQR 27-60). At enrollment, median (IQR) ELF was 14.3 (9.5, 22.1); 586 (37%) and 247 (16%) patients had ELF scores consistent with F3 and F4 fibrosis, respectively. Median LS by TE was 9.9 kPa (9.2, 10.8); 761 (57%) and 227 (17%) patients had LS consistent with F3 and F4 fibrosis, respectively. As of May 2019, median duration of follow-up after registry enrollment was 123 weeks (IQR 96, 168). At week 144, 49% of those with baseline CPT class B/C had improved CPT class, while 98% of those with baseline CPT class A remained in CPT class A. During follow-up, changes in ELF and LS by TE suggested fibrosis improvement in an increasing proportion of patients with both F3 and F4 fibrosis at enrollment (Figure 1). ELF score improved by >0.5 units at week 144 in 27% and 47% of patients with baseline F3 and F4 fibrosis, respectively. Predictors of ELF improvement included higher ELF (P<0.001) and AST (P=0.049), and lower platelets (P=0.02) and BMI (P=0.10) at registry baseline. Conclusions: In patients with cirrhosis in whom HCV has been eradicated by SOF-based therapy, NITs suggest significant fibrosis improvement in 25-50% of patients within 3 years. Associations between reductions in these NITs and improvements in clinical outcomes require evaluation during longer-term follow-up.

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