Journal of Hepatology 50 (2009) 621–624 www.elsevier.com/locate/jhep
Letters to the Editor
Progression of HCV infection in patients with chronic kidney disease To the Editor: We read with great interest the excellent review by Martin and Fabrizi [1] 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]. 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]. 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 [2–4] not commented on in the review [1]. For example, Hu et al. [2] 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 [3,4], 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] 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]. 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]. Interestingly, in a study we have published in abstract form [8], 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 (DCr), necroinflammation (Dgrade) and fibrosis (Dstage) between consecutive LB, were recorded. We found that the patients with stable or worse Cr (DCr P 0) between the 1st and 2nd LB, compared to the patients with Cr improvement (DCr < 0), had less severe yearly progression in fibrosis (mean Dstage/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 (Dstage/year: 0.11 vs 0.74, p = 0.037). Based on the findings in the pre-(2–4) and post-LT setting [8], 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.
References [1] Martin P, Fabrizi F. Hepatitis C virus and kidney disease. J Hepatol 2008;49:613–624. [2] Hu KQ, Lee SM, Hu SX, Xia VW, Hillebrand DJ, Kyulo NL. Clinical presentation of chronic hepatitis C in patients with endstage renal disease and on hemodialysis versus those with normal renal function. Am J Gastroenterol 2005;100:2010–2018. [3] Cotler SJ, Diaz G, Gundlapalli S, Jakate S, Chawla A, Mital D, et al. Characteristics of hepatitis C in renal transplant candidates. J Clin Gastroenterol 2002;35:191–195. [4] Luzar 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;50:157–160.
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Letters to the Editor / Journal of Hepatology 50 (2009) 621–624
[5] Martin P, Carter D, Fabrizi F, Dixit V, Conrad AJ, Artinian L, et al. Histopathological features of hepatitis C in renal transplant candidates. Transplantation 2000;69:1479–1484. [6] Samonakis DN, Cholongitas E, Triantos CK, Griffiths P, Dhillon AP, Thalheimer U, et al. Sustained, spontaneous disappearance of serum HCV-RNA under immunosuppression after liver transplantation for HCV cirrhosis. J Hepatol 2005;43:1091–1093. [7] Roche B, Samuel D. Risk factors for hepatitis C recurrence after liver transplantation. J Viral Hepat 2007;14 (Suppl. 1): 89–96. [8] Cholongitas E, Quaglia A, Samonakis DN, 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:S58.
Evangelos Cholongitas Pinelopi Manousou Dimitrios Samonakis Andrew K. Burroughs * The Royal Free Sheila Sherlock Liver Centre and Department of Surgery, Royal Free Hospital, Pond Street, Hampstead, London NW3 2QG, UK * Tel.: +44 20 74726229; fax: +44 20 74726226. E-mail address:
[email protected] (A.K. Burroughs). doi:10.1016/j.jhep.2008.12.003
Progression of HCV infection in patients with chronic kidney disease: Reply To the Editor: We thank Dr. Cholongitas and colleagues for their comments on our recent review in this Journal on HCV in patients with chronic kidney disease (CKD) and for highlighting findings from other groups who have performed liver biopsies in these patients. As they note we had suggested in a paper several years ago that hemodialysis or perhaps uremia may provide some protective effect against fibrosis development in patients with HCV infection [1]. As cited in our paper, an international group of hepatologists and nephrologists has developed guidelines, under the auspices of the National Kidney Foundation, to guide the management of patients with CKD and HCV infection [2]. Prospective studies with serial liver biopsies are clearly required in this patient population to further define the natural history of HCV infection at various stages of CKD including post renal transplantation particularly as treatment options for HCV expand.
References [1] P.Martin, D.Carter, F.Fabrizi, V.Dixit, A.J.Conrad, L.Artinian, et alHistopathological features of hepatitis C in renal transplant candidatesTransplantation 2000;692000:1479–1484. [2] Kidney disease improving global outcomes (KDIGO): clinical practice guidelines for the prevention, diagnosis, evaluation and treatment of hepatitis C in chronic kidney disease. Kidney Int 2008;109:S1–99.
Paul Martin Fabrizio Fabrizi Center for Liver Diseases, University of Miami, 1500 NW 12th Ave., 31101 Miami, FL 33136, USA Division of Nephrology and Dialysis, Maggiore Hospital, IRCCS Foundation, Milan, Italy E-mail address:
[email protected]
doi:10.1016/j.jhep.2008.12.002
Hepatitis E virus as an emerging cause of chronic liver disease in organ transplant recipients To the Editor: We read with great interest the very complete and upto-date review by R.H. Purcell and S.U. Emerson on hepatitis E virus (HEV) [1]. It highlights that this virus is the leading or the second leading cause of acute hepatitis in adults in many parts of the developing world, and that an increasing number of sporadic autochthonous acute hepatitis E cases have been recently reported
in industrialized countries [1]. Unexpectedly, a new clinical feature has just been described in association with autochthonous hepatitis E virus (HEV) infections in developed countries [2–4]. Indeed, since February 2008, cases of HEV-related chronic hepatitis have been reported in organ transplant recipients by three different teams, including ours. This finding still adds significant interest to hepatitis E, and questions the extent and
