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

doi:10.1111/apt.14404

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

Research output: Contribution to journal › Article › peer-review

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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 language	English
Pages (from-to)	401-411
Number of pages	11
Journal	Alimentary Pharmacology and Therapeutics
Volume	47
Issue number	3
DOIs	https://doi.org/10.1111/apt.14404
Publication status	Published - 1 Feb 2018
Externally published	Yes

Keywords

hepatitis C
Antiviral therapy
decompensated cirrhosis
liver function

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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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

@article{6272b0f36d9f45a7985b0c82ef64fcfd,

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

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.",

keywords = "hepatitis C, Antiviral therapy, decompensated cirrhosis, liver function",

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

year = "2018",

month = feb,

day = "1",

doi = "10.1111/apt.14404",

language = "English",

volume = "47",

pages = "401--411",

journal = "Alimentary Pharmacology and Therapeutics",

issn = "0269-2813",

publisher = "BLACKWELL PUBLISHERS INC",

number = "3",

}

McCaughan, GW, Thwaites, PA, Roberts, SK, Strasser, SI, Mitchell, J, Morales, B, Mason, S, Gow, P, Wigg, A, Tallis, C, Jeffrey, G, George, J, Thompson, AJ, Parker, FC, Angus, PW & 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, vol. 47, no. 3, pp. 401-411. https://doi.org/10.1111/apt.14404

TY - JOUR

T1 - Sofosbuvir and daclatasvir therapy in patients with hepatitis C-related advanced decompensated liver disease (MELD ≥ 15)

AU - McCaughan, G. W.

AU - Thwaites, P. A.

AU - Roberts, S. K.

AU - Strasser, S. I.

AU - Mitchell, J.

AU - Morales, B.

AU - Mason, S.

AU - Gow, P.

AU - Wigg, A.

AU - Tallis, C.

AU - Jeffrey, G.

AU - George, J.

AU - Thompson, A. J.

AU - Parker, F. C.

AU - Angus, P. W.

AU - Australian Liver Association Clinical Research Network

PY - 2018/2/1

Y1 - 2018/2/1

N2 - 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.

AB - 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.

KW - hepatitis C

KW - Antiviral therapy

KW - decompensated cirrhosis

KW - liver function

UR - http://www.scopus.com/inward/record.url?scp=85037328402&partnerID=8YFLogxK

U2 - 10.1111/apt.14404

DO - 10.1111/apt.14404

M3 - Article

C2 - 29205432

AN - SCOPUS:85037328402

SN - 0269-2813

VL - 47

SP - 401

EP - 411

JO - Alimentary Pharmacology and Therapeutics

JF - Alimentary Pharmacology and Therapeutics

IS - 3

ER -

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

Abstract

Keywords

UN SDGs

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