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

Hepatitis C is a disease of the liver caused by the hepatitis C virus (HCV) which spreads from person to person through blood contact which is a result of sharing drug needles, and other items contaminated with blood. This virus remains in the body for a long time and can affect the liver causing its slow destruction or cirrhosis and liver cancer. Infected people may have weakness, nausea, jaundice and lose weight. On blood tests they may have increase in liver enzymes and bilirubin.

HCV is present worldwide and varies among countries with a total of 170 million people infected and constitutes 40% of patients of chronic liver disease. People who are on haemodialysis for long periods have higher chance of getting this infection. It has to be treated before the kidney patient undergoes kidney transplant because some medicines used for its treatment can cause rejection of the transplanted kidney. There are three main treatments for this infection. Two are injections of standard interferon or pegylated interferon given under the skin three times a week or once a week respectively. Treatment needs to be continued for at least 24 to 48 weeks. Along with either of these injections, tablets of ribavirin can be given to improve the results. However ribavirin can accumulate in kidney patients and cause destruction of red blood cells and anaemia.

This review collates the available evidence from standardised studies for treatment of HCV in dialysis patients and did not include uncontrolled studies. Ten studies all in haemodialysis with about 300 patients showed that standard interferon was effective in producing a short term response which was not sustained and was well tolerated.

Pegylated interferon was more effective than standard interferon in producing a short-term response but not a sustained one and both were equally tolerated. Increasing the dose of pegylated interferon did not improve response but was tolerated. Addition of ribavirin to interferon resulted in more treatment discontinuation. Adverse effects of interferons include flu like symptoms, sleep disturbances, decreased appetite, vomiting, diarrhoea or constipation, hair loss and low blood counts. Limitations of this review are that only a few studies were available with few participants, and patients with serious disease were excluded from studies in anticipation of side effects. Hence evidence available was not of high quality.

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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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 strategy: 

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.

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