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


OBJECTIVE
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.


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.


METHODS
Randomised controlled trials (RCTs), quasi-RCTs, first period of randomised cross-over studies on interventions for HCV in CKD on dialysis were considered.


METHODS
We used standard methodological procedures expected by the Cochrane Collaboration and also collected adverse effects data listed in included RCTs.


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.


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.
Department of Nephrology, Kasturba Medical College and Hospital Manipal, Manipal University, PO Box 7 Madhav Nagar, Manipal, Karnataka, India, 576104.
Ravindra A
RA
Prabhu
Sreekumar
S
Nair
Ganesh
G
Pai
Nageswara P
NP
Reddy
Deepak
D
Suvarna
D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D007372:Interferons / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000627:therapeutic use; D012008:Recurrence; D006435:Renal Dialysis / Q000379:methods*; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000401:mortality / Q000628:therapy*; D012254:Ribavirin / Q000627:therapeutic use; D028761:Withholding Treatment / Q000706:statistics & numerical data
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D007372:Interferons; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a