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

G. W. McCaughan, P. A. Thwaites, S. K. Roberts, S. I. Strasser, J. Mitchell, B. Morales, S. Mason, P. Gow, A. Wigg, C. Tallis, G. Jeffrey, J. George, A. J. Thompson, F. C. Parker, P. W. Angus, Australian Liver Association Clinical Research Network

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Abstract

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 (SVR12), 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 SVR12 rate was 70% (76/108). Seventy-eight patients completed 24-weeks therapy. SVR12 was achieved in 56 of these patients on per-protocol-analysis (76%). SVR12 was 80% in genotype 1 compared to 69% in genotype 3. Thirty patients failed to complete therapy. In patients achieving SVR12, median MELD and Child-Pugh fell from 16(IQR15-17) 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: SVR12 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.

Original languageEnglish
Pages (from-to)401-411
Number of pages11
JournalAlimentary Pharmacology and Therapeutics
Volume47
Issue number3
DOIs
Publication statusPublished - 1 Feb 2018
Externally publishedYes

Keywords

  • hepatitis C
  • Antiviral therapy
  • decompensated cirrhosis
  • liver function

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    McCaughan, G. W., Thwaites, P. A., Roberts, S. K., Strasser, S. I., Mitchell, J., Morales, B., Mason, S., Gow, P., Wigg, A., Tallis, C., Jeffrey, G., George, J., Thompson, A. J., Parker, F. C., Angus, P. W., & Australian Liver Association Clinical Research Network (2018). Sofosbuvir and daclatasvir therapy in patients with hepatitis C-related advanced decompensated liver disease (MELD ≥ 15). Alimentary Pharmacology and Therapeutics, 47(3), 401-411. https://doi.org/10.1111/apt.14404