Progression of HCV infection in patients with chronic kidney disease
Authors: Evangelos Cholongitas, Pinelopi Manousou, Dimitrios Samonakis, Andrew K. Burroughs
Journal: Journal of Hepatology (2008)

To the Editor: We read with great interest the excellent review by Martin and Fabrizi [[1]Martin P. Fabrizi F. Hepatitis C virus and kidney disease.J Hepatol. 2008; 49: 613-624Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar] recently published in Journal of Hepatology, regarding the HCV infection in patients with chronic kidney disease (CKD). Rightly, the authors emphasized that advanced fibrosis is a common histologic finding in this group of patients despite ‘normal’ aminotransferase values, making liver biopsy (LB) mandatory for accurate assessment of the liver damage [[1]Martin P. Fabrizi F. Hepatitis C virus and kidney disease.J Hepatol. 2008; 49: 613-624Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar]. The authors also commented on previous published studies, which found no significant difference in fibrosis in chronic hepatitis C (CHC) patients with or without CKD [[1]Martin P. Fabrizi F. Hepatitis C virus and kidney disease.J Hepatol. 2008; 49: 613-624Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar]. However, we feel further comment and clarification is necessary about this issue, since others have found a lower incidence of severe fibrosis in CHC patients with CKD in reports [2Hu K.Q. Lee S.M. Hu S.X. Xia V.W. Hillebrand D.J. Kyulo N.L. Clinical presentation of chronic hepatitis C in patients with end-stage renal disease and on hemodialysis versus those with normal renal function.Am J Gastroenterol. 2005; 100: 2010-2018Crossref PubMed Scopus (32) Google Scholar, 3Cotler S.J. Diaz G. Gundlapalli S. Jakate S. Chawla A. Mital D. et al.Characteristics of hepatitis C in renal transplant candidates.J Clin Gastroenterol. 2002; 35: 191-195Crossref PubMed Scopus (72) Google Scholar, 4Luzar B. Ferlan-Marolt V. Brinovec V. Lesnicar G. Klopcic U. Poljak M. Does end-stage kidney failure influence hepatitis C progression in hemodialysis patients?.Hepatogastroenterology. 2003; 50: 157-160PubMed Google Scholar] not commented on in the review [[1]Martin P. Fabrizi F. Hepatitis C virus and kidney disease.J Hepatol. 2008; 49: 613-624Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar]. For example, Hu et al. [[2]Hu K.Q. Lee S.M. Hu S.X. Xia V.W. Hillebrand D.J. Kyulo N.L. Clinical presentation of chronic hepatitis C in patients with end-stage renal disease and on hemodialysis versus those with normal renal function.Am J Gastroenterol. 2005; 100: 2010-2018Crossref PubMed Scopus (32) Google Scholar] compared 91 CHC patients with end-stage renal disease on dialysis and 159 CHC patients with normal renal function. Those with renal disease had less detectable hepatic fibrosis (i.e. from stage 1 to 4 according to modified Knodell’s scoring system) and advanced fibrosis (i.e. stages 3–4), compared to those without renal dysfunction. These findings confirm previous studies [3Cotler S.J. Diaz G. Gundlapalli S. Jakate S. Chawla A. Mital D. et al.Characteristics of hepatitis C in renal transplant candidates.J Clin Gastroenterol. 2002; 35: 191-195Crossref PubMed Scopus (72) Google Scholar, 4Luzar B. Ferlan-Marolt V. Brinovec V. Lesnicar G. Klopcic U. Poljak M. Does end-stage kidney failure influence hepatitis C progression in hemodialysis patients?.Hepatogastroenterology. 2003; 50: 157-160PubMed Google Scholar], in which the histological lesions were less severe in CHC patients with CKD receiving haemodialysis, compared to those without CKD. In addition, Martin et al. [[5]Martin P. Carter D. Fabrizi F. Dixit V. Conrad A.J. Artinian L. et al.Histopathological features of hepatitis C in renal transplant candidates.Transplantation. 2000; 69: 1479-1484Crossref PubMed Scopus (99) Google Scholar] reported that the severity of histologic damage was less in dialysed patients than pre-dialysis CKD patients with CHC. Although there is no clear explanation, there has been speculation that hemodialysis or uremic serum per se may lead to viral suppression. Our recent report supports this hypothesis. We described 2 patients with recurrent HCV infection after liver transplantation (LT) in whom the HCV RNA by PCR became permanently negative without antiviral therapy several years after transplantation [[6]Samonakis D.N. Cholongitas E. Triantos C.K. Griffiths P. Dhillon A.P. Thalheimer U. et al.Sustained, spontaneous disappearance of serum HCV-RNA under immunosuppression after liver transplantation for HCV cirrhosis.J Hepatol. 2005; 43: 1091-1093Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar]. Both patients were under sirolimus administration and had developed CKD, one due to nephrotic syndrome and one due to tacrolimus nephrotoxicity. Patients who are transplanted for HCV-related cirrhosis nearly all develop recurrent HCV infection post-LT, which has negative impact on post-LT outcome. Although several studies have shown that the course of recurrent HCV is compressed and more aggressive, the precise factors which affect this course after LT have not been completely elucidated [[7]Roche B. Samuel D. Risk factors for hepatitis C recurrence after liver transplantation.J Viral Hepat. 2007; 14: 89-96Crossref PubMed Scopus (83) Google Scholar]. Interestingly, in a study we have published in abstract form [[8]Cholongitas E. Quaglia A. Samonakis D.N. Papatheodoridis G. Senzolo M. Triantos C. et al.Patients with recurrent HCV infection and renal dysfunction after liver transplantation have slower fibrosis progression.J Hepatol. 2006; 44: S58Abstract Full Text PDF Scopus (1) Google Scholar], we found that the presence of renal dysfunction in patients with recurrent HCV after LT was associated with slower progression of fibrosis. In particular, we evaluated 102 consecutive patients, and in each, the changes in serum creatinine (ΔCr), necroinflammation (Δgrade) and fibrosis (Δstage) between consecutive LB, were recorded. We found that the patients with stable or worse Cr (ΔCr ⩾ 0) between the 1st and 2nd LB, compared to the patients with Cr improvement (ΔCr < 0), had less severe yearly progression in fibrosis (mean Δstage/year: 0.28 vs 0.65, respectively, p = 0.05) despite similar clinical (e.g. immunosuppressive therapy) or laboratory (e.g. aminotransferases) characteristics. Interestingly, the patients with CKD, compared to those who maintained normal creatinine values long-term, had significantly slower fibrosis progression (Δstage/year: 0.11 vs 0.74, p = 0.037). Based on the findings in the pre-(2–4) and post-LT setting [[8]Cholongitas E. Quaglia A. Samonakis D.N. Papatheodoridis G. Senzolo M. Triantos C. et al.Patients with recurrent HCV infection and renal dysfunction after liver transplantation have slower fibrosis progression.J Hepatol. 2006; 44: S58Abstract Full Text PDF Scopus (1) Google Scholar], we believe that further evaluation is needed in order to elucidate the exact association between the severity of HCV and CKD, which may have significant implications for new interventions in these patients.