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Editorial perspective:
Kidney Transplant Recipients With Chronic HCV Infection: A Population to prioritize for HCV cure
Pr Stanislas Pol
Necker Hospital - Paris

HCV treatment should be given in priority in patients with stage 4-5 chronic kidney disease (CKD) and in kidney recipients because:

  1. HCV increases the incidence and the prevalence of renal disease, end-stage renal disease (ESRD) and  ESRD-related mortality in general population(1-2) and cumulative incidence of ESRD decreases with HCV treatment (3)
  2. Despite the introduction of screening, improved lifestyle and prevention measures HCV prevalence, even if significantly decreasing, is higher than in general population in candidates for transplantation (4);
  3.  HCV increases the risk of mortality in dialysis patients (5-6);
  4. Transplant recipients with HCV infection have lower survival than HCV non-infected ones, mainly for liver disease or septic complications due to cirrhosis and/or immunosuppressive therapy (7) and this remains true in the more recent data (8);
  5. HCV impairs renal allograft survival due to de novo membrano-proliferative glomerulonephritis and may even perhaps favour chronic allograft rejection (9)
  6. HCV antiboby positivity increases the incidence of HCC in kidney recipients (10).
  7. HCV RNA undetectability, which was usually achieved before transplantation, improves patient and allograft survival (8).
  8. Three phase 3 studies with different anti-HCV combinations have know been published, showing sustained virologic response in patients with stage 4-5 CKD of 90% in 20 genotype 1 patients receiving ombitasvir/paritaprevir/ritonavir + dasabuvir and ribavirin for 12 weeks (11) and 99% in 111 Genotype 1 patients treated 12 weeks with elbasvir/grazoprevir (12), and now, in a recent paper by Colombo and al (13), 100% cure rate with 12 weeks of ledipasvir/sofosbuvir for 12 weeks in 57 patients with history of kidney transplantation and either genotype 1 (n=51) or 4 (n=6).

The helpful KDIGO recommendations devoted to Hepatitis C in CKD and published in 2008-2009 (14) has taken these harmful consequences into account. There is an urgent need to update these guidelines but we are still awaiting their availability.
Given the incredible DAAs revolution, the main issues are: 1. to decide when to treat those patients, before or after renal transplantation; 2. to define the best therapeutic option.
Anti-HCV therapy should be considered in all patients with symptomatic cryoglobulinemic vasculitis which is seen in a third of patients with renal involvement. DAAs should also be given to all dialysis patients, since HCV infection increases hepatic and extra-hepatic (diabetes, vascular disease) morbidity and mortality in this population regardless fibrosis stage and whether or not candidates for kidney transplantation. Patients with severe renal impairment and significant liver fibrosis, including candidates for kidney transplantation should be considered for antiviral treatment. However, it should be noted that the absence of antiviral therapy might be considered as an opportunity to be transplanted earlier with an HCV-infected allograft for dialysis patients without significant liver fibrosis. Finally anti-HCV therapy should be given to all HCV-infected kidney recipients, with expected benefits which has been recently highlighted (8) and are similar to those reported for HBV (15).

Thus, there is now room and need for more aggressive treatment of HCV in contrast to the current very low treatment rate of HCV in the nephrology setting (16).

References:

  1. Su F-H, et al. Association of hepatitis C virus infection with risk of ESRD: a population-based study. Am J Kidney Dis 2012; 60: 553−560.
  2. Park H, et al. A meta-analytic assessment of the risk of chronic kidney disease in patients with chronic hepatitis C virus infection. J Viral Hepat 2015; 22:897-905.
  3. Hsu YC, et al. Association between antiviral treatment and extrahepatic outcomes in patients with hepatitis C virus infection. Gut 2015; 64: 495t 20.
  4. Fissell R, et al. Patterns of hepatitis C prevalence and seroconversion in hemodialysis units from three continents: The DOPPS. Kidney Int 2004; 65: 2335-42.
  5. Goodkin D, et al. Association of comorbid conditions and mortality in haemodialysis patients in Europe, Japan, and the United States: the dialysis outcomes and practice patterns. J Am Soc Nephrol 2003; 14: 3270-7.F
  6. Fabrizi F, Dixit V, Messa P. Impact of hepatitis C on survival in dialysis patients: a link with cardiovascular mortality? J Viral Hepat 2012; 19: 601-7.
  7. Fabrizi et al. The impact of hepatitis C virus infection on survival in dialysis patients: meta-analysis of observational studies. J Viral Hepat 2007; 14: 697—703.
  8. Fontaine H, et al. Prognostic impact of hepatitis B and C infections in kidney recipients: control of viral replication improves patient and graft survival.
  9. Cruzado J, et al. Hepatitis C virus infection and de novo glomerular lesions in renal allografts. Am J. Transplant 2001; 1: 171-8.
  10. Hoffmann CJ, et al. Incidence and risk factors for hepatocellular carcinoma after solid organ transplantation. Transplantation 2008; 86: 784-90.
  11. 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.
  12. Pockros PJ, et al.  Efficacy of direct-acting dntiviral combination for patients with HCV genotype 1 infection and severe renal impairment or end-stage renal disease. Gastroenterology 2016;150:1590-8.
  13. Colombo M, et al. Ann Intern Med. 2016 Nov 15. doi: 10.7326/M16-1205 Ebub ahead of print.
  14. Kidney Disease: Improving Global Outcomes (KDIGO). KDIGO clinical practice guidelines for the prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease. Kidney Int Suppl 2008; 109: S1-S99.
  15. Cosconea S, et al. Benefits associated with antiviral treatment in kidney allograft recipients with chronic hepatitis B virus infection. J Hepatol 2015; 57: 55-60.
  16. Goodkin DA, et al. Hepatitis C infection is very rarely treated among hemodialysis patients. Am J Nephrol. 2013; 38: 405-412.