Interventions for dialysis patients with hepatitis C virus (HCV) infection

Ravindra A. Prabhu, Sreekumar Nair, Ganesh Pai, Nageswara P. Reddy, Deepak Suvarna

Research output: Contribution to journalReview article

7 Citations (Scopus)

Abstract

Background: Hepatitis C virus (HCV) infection is common in chronic kidney disease (CKD) patients on dialysis, causes chronic liver disease, increases mortality and impacts kidney transplant outcomes. Sustained response to the preferred treatment with standard or pegylated (PEG) interferon is seen in 39% with side effects necessitating treatment discontinuation in 20%. We collated evidence for treatment response and harms of interventions for HCV infection in dialysis. Objectives: We aimed to look at the benefits and harms of various interventions for HCV infection in CKD patients on HD or peritoneal dialysis, specifically on mortality, disease relapse, response to treatment, treatment discontinuation, time to recovery, quality of life, cost effectiveness,adverse effects, and other outcomes. We aimed to study comparisons of available interventions with a placebo or control group, combinations of interventions with placebo or control group, interventions with each other singly and in combination, available standard interventions with newer treatment modalities. Search methods: We searched Cochrane Kidney and Transplant's Specialised Register to 24 March 2015 through contact with the Trials' Search Co-ordinator. We also checked references of reviews, studies and contacted study authors to identify additional studies. Selection criteria: Randomised controlled trials (RCTs), quasi-RCTs, first period of randomised cross-over studies on interventions for HCV in CKD on dialysis were considered. Data collection and analysis: We used standard methodological procedures expected by the Cochrane Collaboration and also collected adverse effects data listed in included RCTs. Main results: Ten RCTs (361 participants) met our inclusion criteria. Five RCTs (152 participants, 134 analysed) with low to moderate quality of evidence compared standard recombinant interferon with placebo or control. There was no significant difference for mortality (5 studies (134 participants): RR 0.89, 95% CI 0.06 to 13.23), relapses (1 study (36 participants): RR 0.72, 95% CI 0.28 to 1.88), sustained virological response (4 studies (98 participants): RR 3.25, 95% CI 0.81 to 13.07), treatment discontinuation (4 studies (116 participants): RR 4.59, 95% CI 0.49 to 42.69) and number with adverse events (5 studies (143 participants): RR 3.56, 95% CI 0.98 to 13.01). End of treatment response was significantly more for standard interferon (5 studies (132 participants): RR 8.62, 95% CI 3.03 to 24.55). There was overall low to unclear risk of bias and no significant heterogeneity. One RCT (50 participants) with moderate quality of evidence compared PEG interferon and standard interferon. There was no significant difference in mortality (RR 0.33, 95% CI 0.01 to 7.81), relapses (RR 0.72, 95% CI 0.41 to 1.25), sustained virological response (RR 2.40, 95% CI 0.99 to 5.81), treatment discontinuation (RR 0.11, 95% CI 0.01 to 1.96) and number with major adverse events (RR 0.11, 95% CI 0.01 to 1.96). End of treatment response was significantly more for PEG interferon (RR 1.53, 95% CI 1.09 to 2.15). There was overall low risk of bias. Two RCTs (97 participants) with moderate quality of evidence compared two doses of two different preparations of PEG interferon. Subgroup analysis comparing high and low doses of PEG interferon alpha-2a (135 μg/week versus 90 μg/week) and PEG interferon alpha-2b (1 μg/kg versus 0.5 μg/kg body weight/week) found no significant difference in mortality (2 studies (97 participants): RR 4.30, 95% CI 0.76 to 24.33), relapses (1 study (81 participants): RR 1.11, 95% CI 0.45 to 2.77), end of treatment response (2 studies (97 participants): RR 1.42, 95% CI 0.51 to 3.90), sustained virological response (2 studies (97 participants): RR 1.19, 95% CI 0.68 to 2.07), treatment discontinuation (2 studies (97 participants): RR 1.20, 95% CI 0.63 to 2.28), patients with adverse events (2 studies (97 participants): RR 1.05, 95% CI 0.61 to 1.83) or serious adverse events (2 studies (97 participants): RR 1.24, 95% CI 0.72 to 2.14). Both had overall low risk of bias and no significant subgroup differences. Two RCTs (62 participants) with moderate quality of evidence compared standard or PEG interferon alone or in combination with ribavirin. The only reported outcome in both was treatment discontinuation which was significantly more with ribavirin in the one study (RR 0.34, 95% CI 0.14 to 0.84) and pooled 7/10 in the second. No RCTs had data on time to recovery, cost-effectiveness, quality of life, and other outcomes and in peritoneal dialysis. Authors' conclusions: Our review demonstrated that in CKD patients on haemodialysis with HCV infection treatment with standard interferon brings about an end of treatment but not a sustained virological response and is relatively well tolerated. PEG interferon is more effective than standard interferon for end of treatment response but not for sustained response; both were equally tolerated. Increasing doses of PEG interferon did not improve responses but high and low doses are equally tolerated. Addition of ribavirin results in more treatment discontinuation.

Original languageEnglish
Article numberCD007003
JournalCochrane Database of Systematic Reviews
Volume2015
Issue number8
DOIs
Publication statusPublished - 19-08-2015

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Virus Diseases
Hepacivirus
Dialysis
Interferons
Randomized Controlled Trials
Therapeutics
Chronic Renal Insufficiency
Ribavirin
Mortality
Recurrence
Placebos
Peritoneal Dialysis
Cost-Benefit Analysis
Quality of Life
Transplants
Kidney
Control Groups
Interferon-alpha
Cross-Over Studies
Patient Selection

All Science Journal Classification (ASJC) codes

  • Pharmacology (medical)

Cite this

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title = "Interventions for dialysis patients with hepatitis C virus (HCV) infection",
abstract = "Background: Hepatitis C virus (HCV) infection is common in chronic kidney disease (CKD) patients on dialysis, causes chronic liver disease, increases mortality and impacts kidney transplant outcomes. Sustained response to the preferred treatment with standard or pegylated (PEG) interferon is seen in 39{\%} with side effects necessitating treatment discontinuation in 20{\%}. We collated evidence for treatment response and harms of interventions for HCV infection in dialysis. Objectives: We aimed to look at the benefits and harms of various interventions for HCV infection in CKD patients on HD or peritoneal dialysis, specifically on mortality, disease relapse, response to treatment, treatment discontinuation, time to recovery, quality of life, cost effectiveness,adverse effects, and other outcomes. We aimed to study comparisons of available interventions with a placebo or control group, combinations of interventions with placebo or control group, interventions with each other singly and in combination, available standard interventions with newer treatment modalities. Search methods: We searched Cochrane Kidney and Transplant's Specialised Register to 24 March 2015 through contact with the Trials' Search Co-ordinator. We also checked references of reviews, studies and contacted study authors to identify additional studies. Selection criteria: Randomised controlled trials (RCTs), quasi-RCTs, first period of randomised cross-over studies on interventions for HCV in CKD on dialysis were considered. Data collection and analysis: We used standard methodological procedures expected by the Cochrane Collaboration and also collected adverse effects data listed in included RCTs. Main results: Ten RCTs (361 participants) met our inclusion criteria. Five RCTs (152 participants, 134 analysed) with low to moderate quality of evidence compared standard recombinant interferon with placebo or control. There was no significant difference for mortality (5 studies (134 participants): RR 0.89, 95{\%} CI 0.06 to 13.23), relapses (1 study (36 participants): RR 0.72, 95{\%} CI 0.28 to 1.88), sustained virological response (4 studies (98 participants): RR 3.25, 95{\%} CI 0.81 to 13.07), treatment discontinuation (4 studies (116 participants): RR 4.59, 95{\%} CI 0.49 to 42.69) and number with adverse events (5 studies (143 participants): RR 3.56, 95{\%} CI 0.98 to 13.01). End of treatment response was significantly more for standard interferon (5 studies (132 participants): RR 8.62, 95{\%} CI 3.03 to 24.55). There was overall low to unclear risk of bias and no significant heterogeneity. One RCT (50 participants) with moderate quality of evidence compared PEG interferon and standard interferon. There was no significant difference in mortality (RR 0.33, 95{\%} CI 0.01 to 7.81), relapses (RR 0.72, 95{\%} CI 0.41 to 1.25), sustained virological response (RR 2.40, 95{\%} CI 0.99 to 5.81), treatment discontinuation (RR 0.11, 95{\%} CI 0.01 to 1.96) and number with major adverse events (RR 0.11, 95{\%} CI 0.01 to 1.96). End of treatment response was significantly more for PEG interferon (RR 1.53, 95{\%} CI 1.09 to 2.15). There was overall low risk of bias. Two RCTs (97 participants) with moderate quality of evidence compared two doses of two different preparations of PEG interferon. Subgroup analysis comparing high and low doses of PEG interferon alpha-2a (135 μg/week versus 90 μg/week) and PEG interferon alpha-2b (1 μg/kg versus 0.5 μg/kg body weight/week) found no significant difference in mortality (2 studies (97 participants): RR 4.30, 95{\%} CI 0.76 to 24.33), relapses (1 study (81 participants): RR 1.11, 95{\%} CI 0.45 to 2.77), end of treatment response (2 studies (97 participants): RR 1.42, 95{\%} CI 0.51 to 3.90), sustained virological response (2 studies (97 participants): RR 1.19, 95{\%} CI 0.68 to 2.07), treatment discontinuation (2 studies (97 participants): RR 1.20, 95{\%} CI 0.63 to 2.28), patients with adverse events (2 studies (97 participants): RR 1.05, 95{\%} CI 0.61 to 1.83) or serious adverse events (2 studies (97 participants): RR 1.24, 95{\%} CI 0.72 to 2.14). Both had overall low risk of bias and no significant subgroup differences. Two RCTs (62 participants) with moderate quality of evidence compared standard or PEG interferon alone or in combination with ribavirin. The only reported outcome in both was treatment discontinuation which was significantly more with ribavirin in the one study (RR 0.34, 95{\%} CI 0.14 to 0.84) and pooled 7/10 in the second. No RCTs had data on time to recovery, cost-effectiveness, quality of life, and other outcomes and in peritoneal dialysis. Authors' conclusions: Our review demonstrated that in CKD patients on haemodialysis with HCV infection treatment with standard interferon brings about an end of treatment but not a sustained virological response and is relatively well tolerated. PEG interferon is more effective than standard interferon for end of treatment response but not for sustained response; both were equally tolerated. Increasing doses of PEG interferon did not improve responses but high and low doses are equally tolerated. Addition of ribavirin results in more treatment discontinuation.",
author = "Prabhu, {Ravindra A.} and Sreekumar Nair and Ganesh Pai and Reddy, {Nageswara P.} and Deepak Suvarna",
year = "2015",
month = "8",
day = "19",
doi = "10.1002/14651858.CD007003.pub2",
language = "English",
volume = "2015",
journal = "Cochrane Database of Systematic Reviews",
issn = "1361-6137",
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}

Interventions for dialysis patients with hepatitis C virus (HCV) infection. / Prabhu, Ravindra A.; Nair, Sreekumar; Pai, Ganesh; Reddy, Nageswara P.; Suvarna, Deepak.

In: Cochrane Database of Systematic Reviews, Vol. 2015, No. 8, CD007003, 19.08.2015.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Interventions for dialysis patients with hepatitis C virus (HCV) infection

AU - Prabhu, Ravindra A.

AU - Nair, Sreekumar

AU - Pai, Ganesh

AU - Reddy, Nageswara P.

AU - Suvarna, Deepak

PY - 2015/8/19

Y1 - 2015/8/19

N2 - Background: Hepatitis C virus (HCV) infection is common in chronic kidney disease (CKD) patients on dialysis, causes chronic liver disease, increases mortality and impacts kidney transplant outcomes. Sustained response to the preferred treatment with standard or pegylated (PEG) interferon is seen in 39% with side effects necessitating treatment discontinuation in 20%. We collated evidence for treatment response and harms of interventions for HCV infection in dialysis. Objectives: We aimed to look at the benefits and harms of various interventions for HCV infection in CKD patients on HD or peritoneal dialysis, specifically on mortality, disease relapse, response to treatment, treatment discontinuation, time to recovery, quality of life, cost effectiveness,adverse effects, and other outcomes. We aimed to study comparisons of available interventions with a placebo or control group, combinations of interventions with placebo or control group, interventions with each other singly and in combination, available standard interventions with newer treatment modalities. Search methods: We searched Cochrane Kidney and Transplant's Specialised Register to 24 March 2015 through contact with the Trials' Search Co-ordinator. We also checked references of reviews, studies and contacted study authors to identify additional studies. Selection criteria: Randomised controlled trials (RCTs), quasi-RCTs, first period of randomised cross-over studies on interventions for HCV in CKD on dialysis were considered. Data collection and analysis: We used standard methodological procedures expected by the Cochrane Collaboration and also collected adverse effects data listed in included RCTs. Main results: Ten RCTs (361 participants) met our inclusion criteria. Five RCTs (152 participants, 134 analysed) with low to moderate quality of evidence compared standard recombinant interferon with placebo or control. There was no significant difference for mortality (5 studies (134 participants): RR 0.89, 95% CI 0.06 to 13.23), relapses (1 study (36 participants): RR 0.72, 95% CI 0.28 to 1.88), sustained virological response (4 studies (98 participants): RR 3.25, 95% CI 0.81 to 13.07), treatment discontinuation (4 studies (116 participants): RR 4.59, 95% CI 0.49 to 42.69) and number with adverse events (5 studies (143 participants): RR 3.56, 95% CI 0.98 to 13.01). End of treatment response was significantly more for standard interferon (5 studies (132 participants): RR 8.62, 95% CI 3.03 to 24.55). There was overall low to unclear risk of bias and no significant heterogeneity. One RCT (50 participants) with moderate quality of evidence compared PEG interferon and standard interferon. There was no significant difference in mortality (RR 0.33, 95% CI 0.01 to 7.81), relapses (RR 0.72, 95% CI 0.41 to 1.25), sustained virological response (RR 2.40, 95% CI 0.99 to 5.81), treatment discontinuation (RR 0.11, 95% CI 0.01 to 1.96) and number with major adverse events (RR 0.11, 95% CI 0.01 to 1.96). End of treatment response was significantly more for PEG interferon (RR 1.53, 95% CI 1.09 to 2.15). There was overall low risk of bias. Two RCTs (97 participants) with moderate quality of evidence compared two doses of two different preparations of PEG interferon. Subgroup analysis comparing high and low doses of PEG interferon alpha-2a (135 μg/week versus 90 μg/week) and PEG interferon alpha-2b (1 μg/kg versus 0.5 μg/kg body weight/week) found no significant difference in mortality (2 studies (97 participants): RR 4.30, 95% CI 0.76 to 24.33), relapses (1 study (81 participants): RR 1.11, 95% CI 0.45 to 2.77), end of treatment response (2 studies (97 participants): RR 1.42, 95% CI 0.51 to 3.90), sustained virological response (2 studies (97 participants): RR 1.19, 95% CI 0.68 to 2.07), treatment discontinuation (2 studies (97 participants): RR 1.20, 95% CI 0.63 to 2.28), patients with adverse events (2 studies (97 participants): RR 1.05, 95% CI 0.61 to 1.83) or serious adverse events (2 studies (97 participants): RR 1.24, 95% CI 0.72 to 2.14). Both had overall low risk of bias and no significant subgroup differences. Two RCTs (62 participants) with moderate quality of evidence compared standard or PEG interferon alone or in combination with ribavirin. The only reported outcome in both was treatment discontinuation which was significantly more with ribavirin in the one study (RR 0.34, 95% CI 0.14 to 0.84) and pooled 7/10 in the second. No RCTs had data on time to recovery, cost-effectiveness, quality of life, and other outcomes and in peritoneal dialysis. Authors' conclusions: Our review demonstrated that in CKD patients on haemodialysis with HCV infection treatment with standard interferon brings about an end of treatment but not a sustained virological response and is relatively well tolerated. PEG interferon is more effective than standard interferon for end of treatment response but not for sustained response; both were equally tolerated. Increasing doses of PEG interferon did not improve responses but high and low doses are equally tolerated. Addition of ribavirin results in more treatment discontinuation.

AB - Background: Hepatitis C virus (HCV) infection is common in chronic kidney disease (CKD) patients on dialysis, causes chronic liver disease, increases mortality and impacts kidney transplant outcomes. Sustained response to the preferred treatment with standard or pegylated (PEG) interferon is seen in 39% with side effects necessitating treatment discontinuation in 20%. We collated evidence for treatment response and harms of interventions for HCV infection in dialysis. Objectives: We aimed to look at the benefits and harms of various interventions for HCV infection in CKD patients on HD or peritoneal dialysis, specifically on mortality, disease relapse, response to treatment, treatment discontinuation, time to recovery, quality of life, cost effectiveness,adverse effects, and other outcomes. We aimed to study comparisons of available interventions with a placebo or control group, combinations of interventions with placebo or control group, interventions with each other singly and in combination, available standard interventions with newer treatment modalities. Search methods: We searched Cochrane Kidney and Transplant's Specialised Register to 24 March 2015 through contact with the Trials' Search Co-ordinator. We also checked references of reviews, studies and contacted study authors to identify additional studies. Selection criteria: Randomised controlled trials (RCTs), quasi-RCTs, first period of randomised cross-over studies on interventions for HCV in CKD on dialysis were considered. Data collection and analysis: We used standard methodological procedures expected by the Cochrane Collaboration and also collected adverse effects data listed in included RCTs. Main results: Ten RCTs (361 participants) met our inclusion criteria. Five RCTs (152 participants, 134 analysed) with low to moderate quality of evidence compared standard recombinant interferon with placebo or control. There was no significant difference for mortality (5 studies (134 participants): RR 0.89, 95% CI 0.06 to 13.23), relapses (1 study (36 participants): RR 0.72, 95% CI 0.28 to 1.88), sustained virological response (4 studies (98 participants): RR 3.25, 95% CI 0.81 to 13.07), treatment discontinuation (4 studies (116 participants): RR 4.59, 95% CI 0.49 to 42.69) and number with adverse events (5 studies (143 participants): RR 3.56, 95% CI 0.98 to 13.01). End of treatment response was significantly more for standard interferon (5 studies (132 participants): RR 8.62, 95% CI 3.03 to 24.55). There was overall low to unclear risk of bias and no significant heterogeneity. One RCT (50 participants) with moderate quality of evidence compared PEG interferon and standard interferon. There was no significant difference in mortality (RR 0.33, 95% CI 0.01 to 7.81), relapses (RR 0.72, 95% CI 0.41 to 1.25), sustained virological response (RR 2.40, 95% CI 0.99 to 5.81), treatment discontinuation (RR 0.11, 95% CI 0.01 to 1.96) and number with major adverse events (RR 0.11, 95% CI 0.01 to 1.96). End of treatment response was significantly more for PEG interferon (RR 1.53, 95% CI 1.09 to 2.15). There was overall low risk of bias. Two RCTs (97 participants) with moderate quality of evidence compared two doses of two different preparations of PEG interferon. Subgroup analysis comparing high and low doses of PEG interferon alpha-2a (135 μg/week versus 90 μg/week) and PEG interferon alpha-2b (1 μg/kg versus 0.5 μg/kg body weight/week) found no significant difference in mortality (2 studies (97 participants): RR 4.30, 95% CI 0.76 to 24.33), relapses (1 study (81 participants): RR 1.11, 95% CI 0.45 to 2.77), end of treatment response (2 studies (97 participants): RR 1.42, 95% CI 0.51 to 3.90), sustained virological response (2 studies (97 participants): RR 1.19, 95% CI 0.68 to 2.07), treatment discontinuation (2 studies (97 participants): RR 1.20, 95% CI 0.63 to 2.28), patients with adverse events (2 studies (97 participants): RR 1.05, 95% CI 0.61 to 1.83) or serious adverse events (2 studies (97 participants): RR 1.24, 95% CI 0.72 to 2.14). Both had overall low risk of bias and no significant subgroup differences. Two RCTs (62 participants) with moderate quality of evidence compared standard or PEG interferon alone or in combination with ribavirin. The only reported outcome in both was treatment discontinuation which was significantly more with ribavirin in the one study (RR 0.34, 95% CI 0.14 to 0.84) and pooled 7/10 in the second. No RCTs had data on time to recovery, cost-effectiveness, quality of life, and other outcomes and in peritoneal dialysis. Authors' conclusions: Our review demonstrated that in CKD patients on haemodialysis with HCV infection treatment with standard interferon brings about an end of treatment but not a sustained virological response and is relatively well tolerated. PEG interferon is more effective than standard interferon for end of treatment response but not for sustained response; both were equally tolerated. Increasing doses of PEG interferon did not improve responses but high and low doses are equally tolerated. Addition of ribavirin results in more treatment discontinuation.

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