Managing dialysis patients with hepatitis C infection

Hepatitis C infection is a major bugbear of dialysis patients throughout the developing world. About 10 years ago, dialysis units were reporting very high prevalence – going up to 75% in some instances. With improvement in infection control practices, this prevalence has come down in recent years. Even then, a large number of unfortunate patients fall victim of this malady for no fault of their own. It is common knowledge that this is due to horizontal transmission in dialysis units.

It is not unusual for patients who are in the process of being worked up for a transplant contract this infection which effectively either ruins their chances of getting a transplant, leads to substantial delays, adds to the cost of therapy and puts them at risk of developing liver disease after transplantation. The available therapies have been costly, difficult to administer and not easy to tolerate for patients. With the advent of the direct acting anti-viral agents (DAA), especially combinations, this scenario is set to change. Most of these combinations have a high antiviral potency (SVR >90%) and good tolerance. International guidelines recommend to treat all infected patients.

The available drugs include:

  • Nonstructural proteins 3/4A (NS3/4A) protease inhibitors
    – Grazoprevir, Paritaprevir, Simeprevir
  • NS5A INHIBITORS
    – Daclatasvir, Elbasvir, Ledipasvir, Ombitasvir
  • NS5B nucleoside polymerase inhibitors
    Nucleot(s)ide polymerase inhibitors (NPIs)
    – Sofosbuvir
    Non-nucleoside polymerase inhibitors (NNPIs)
    – Dasabuvir
  • FIXED-DOSE COMBINATIONS
    – Elbasvir-grazoprevir
    – Ledipasvir-sofosbuvir
    – Ombitasvir-paritaprevir-ritonavir with or without dasabuvir

Mechanism of action:

HCV

Despite excellent efficacy, there is  uncertainty on how to best use these agents for patients with advanced kidney disease, including those on dialysis. The clinical practice guidelines are from another era and hence not helpful. The good news is that this is likely to change soon. The KDIGO Hepatitis C Clinical Practice Guidelines are set to be updated. In the interim, a group of experts have provided some advice on how should these agents be used. Given that one of the authors of this paper is the Chair of the KDIGO Work Group, it gives a fair window into how the guidelines will shape up. The recommendations from these authors are summarised below:

  • Stage 4-5 CKD patients with HCV infection should be treated because
    HCV increases the risk of kidney disease progression.
    HCVdecreases survival in dialysis and transplant patients
    HCV increases the risk of HCC
    HCV increases the risk of NODAT, CVD, stroke and extra hepatic cancers
  • Liver biopsy is not needed to decide treatment. Liver fibrosis should be evaluated mostly non invasively.
  • The following patients should receive DAA
    All patients with HCV-cryoglobulinemic vasculitis
    All HCV-infected dialysis patients
    All HCV-infected kidney transplant recipients
  • The best regimen for patients with renal impairment is unknown
  • A combination of grazoprevir and elbasvir (does not require dose adjustment) led to 99% SVR in a RCT of genotype 1–infected patients with CKD stage 4–5
  • Anecdotal results with compassionate use are excellent.
    Two pilot studies reported 100% SVR in kidney transplant recipients treated with sofosbuvir-based antiviral therapy with or without ribavirin.
  • Simeprevi or daclatasvir work best in combination with sofosbuvir
  • Low-dose Sofosbuvir monotherapy gives poor results

Should patients with hepatitis C infection on dialysis be treated with direct acting antiviral agents?

View Results

Loading ... Loading ...

9 thoughts on “Managing dialysis patients with hepatitis C infection

  1. J.J.Singh

    I have treated 1 pt. of genotype1 with alt. day sofosubir and daily daclatazavir x3mths with SVR(target not detected)at the end of 3 mths.

    Reply
  2. vjha Post author

    For those who are looking for more evidence –

    Roth D, et al. Grazoprevir plus elbasvir in treatment-naive and treatment-experienced patients with hepatitis C virus genotype 1 infection and stage 4-5 chronic kidney disease (the C-SURFER study): a combination phase 3 study. Lancet. 2015 Oct 17;386(10003):1537-45.

    Main findings (in authors’ words):

    This study is the first phase 3 study to assess an interferon-free, ribavirin-free, all-oral treatment regimen for patients with HCV infection and advanced (stage 4–5) chronic kidney disease. Patients receiving grazoprevir plus elbasvir for 12 weeks had a low rate of adverse events compared with a deferred treament group and achieved a 99% SVR12 compared with a historical control. Data from the present study suggest that the availability of a grazoprevir and elbasvir regimen for patients with stage 4–5 chronic kidney disease could represent a marked improvement in treatment for this significantly underserved patient group.

    An accompanying commentary (by Michel Jadoul, Co-chair of the Hep C Guideline Work group) says:

    A much greater fraction of patients with chronic kidney disease stages 4 and 5 should soon be treated. By contrast with the expected residence of HCV for decades in dialysis units, it is now time to envision eradication of HCV from such units. Needless to say, this goal should best be achieved by the combination of prevention and cure, rather than by cure only. The long-awaited availability of highly active anti-HCV drugs should be no reason for complacency regarding the application of basic costeffective hygiene precautions within haemodialysis units.

    Strong stuff…..

    Reply
  3. Dr Chaitanya Vemuri

    Respected sir,
    For stable hcv positive esrd patients with mild fibrosis of liver , do you recommend pre transplant antiviral therapy with DAA or post transplant antiviral therapy?
    Which is preferable ?

    Reply
    1. vjha Post author

      I would treat right away – for the longer you leave them untreated the more they are at risk of complications. What would others do?

      Reply
  4. Rajiv Mehta Gastroenterologist

    We are doing one clinical trial with Dr. Ketan Desai at Mahavir hospital. We are using Ribavirin free treatment and full dose of Sofosbuvir with Ledipasvir in Genotype 1 and Sofosbuvir Plus Declatazavir for Genotype 3. So far good RVR. No major problem.

    Reply
  5. Vijay kher

    I have started using sofosobuvir 400 mg thrice a week taken before dialysis with ribavarin 400 to 600 mg depending on tolerable dose of ribavarin in dialysis patients and have seen rapid viral response in all patients.Long term outcomes are awaited Seven patients have completed 3 months treatment.
    No withdrawal due to adverse events.
    Tansplant patients we r using sofosobuvir and ledepsavir combination now .initially used sofo with ribavarin.Short term results with response rates of more than 95%.one patient relapsed after 3 months of completing sofo and ribavarin course.Is now on sofo plus ledipasvir.is become hcv negative.These r early days yet.

    Reply
  6. Dr Syed Munib

    I have started pre & post Renal Transplant patients on sofosbuvir & to Ribavirin with good result and almost no complications except low Hb which we built up & maintain it. Now the prices are also drastically lower so most of these patients can afford it and it is cost effective.

    Reply
  7. Dr Zahid Nabi

    We have started treating our CKD dialysis and transplant patients with sofisbuvir and low dose ribavirin with very good tesults and no obvious complications so i would siggest a more aggressive approach in treating this population

    Reply

Leave a Reply

Your email address will not be published. Required fields are marked *