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)
Non-nucleoside polymerase inhibitors (NNPIs)
- FIXED-DOSE COMBINATIONS
– Ombitasvir-paritaprevir-ritonavir with or without dasabuvir
Mechanism of action:
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