Sofosbuvir and daclatasvir therapy in patients with hepatitis C‐related advanced decompensated liver disease ( MELD MELD ≥ 15)

摘要

Summary Background Antiviral therapy for hepatitis C has the potential to improve liver function in patients with decompensated cirrhosis. Aims To examine the virological response and effect of viral clearance in patients with decompensated hepatitis C cirrhosis all with MELD scores ≥15 following sofosbuvir/daclatasvir ± ribavirin. Methods We prospectively collected data on patients who commenced sofosbuvir/daclatasvir for 24‐weeks under the Australian patient supply program ( TOSCAR ) and analysed outcomes including sustained viral response at 12 weeks ( SVR 12), death and transplant. Results 108 patients (M/F, 79/29; median age 56years; Child‐Pugh 10; MELD 16; genotype 1/3, 55/47) received sofosbuvir/daclatasvir and two also received ribavirin. On intention‐to‐treat, the SVR 12 rate was 70% (76/108). Seventy‐eight patients completed 24‐weeks therapy. SVR 12 was achieved in 56 of these patients on per‐protocol‐analysis (76%). SVR 12 was 80% in genotype 1 compared to 69% in genotype 3. Thirty patients failed to complete therapy. In patients achieving SVR 12, median MELD and Child‐Pugh fell from 16( IQR 15‐17) to 14(12‐17) and 10(9‐11) to 8(7‐9), respectively (P.001). In those who died, MELD increased from 16 to 23 at death (P=.036). Patients who required transplantation had a significantly higher baseline MELD (20) compared to those patients completing treatment (16) (P=.0010). The odds ratio for transplant in patients with baseline MELD ≥20 was 13.8(95% CI 2.78‐69.04). Conclusions SVR 12 rates with sofosbuvir/daclatasvir in advanced liver disease are lower than in compensated disease. Although treatment improves MELD and Child‐Pugh in most patients, a significant proportion will die or require transplantation. In those with MELD ≥20, it may be better to delay treatment until post‐transplant.