Autori: A. Cappoli1, I. Umbro2, D. Palazzo1, E. Biliotti1, A. Bachetoni3, P. Perinelli1, F. TintI2, M.D. D’Alessandro3, S. Grieco1, R. Labriola3, M. Subic1, P. Rucci4 , G. Taliani1, A.P. Mitterhofer
Affiliazioni: 1. Department of Clinical Medicine,2. Department of Anatomical, Histological, Forensic Medicine and Orthopedics, 3. Department of General Surgery, Policlinico Umberto I, Sapienza, University of Rome, 4. Department of Molecular Science, Bologna
Background: Hepatitis C virus (HCV) infection is a major public health problem with an estimated number between 120 and 170 million people infected worldwide. Although in patients with HCV infection and liver disease renal involvement (RI) may be mild or clinically silent HCV is associated with loss of kidney function. There is a recognized association between HCV and glomerular damage whereas tubular damage has not been defined yet. Glomerular lesions associated with HCV have been described in the presence or absence of liver disease; all patients with HCV associated GN have detectable HCV RNA in serum. Regardless of the tubulointerstitial injury associated with glomerular lesions, HCV may lead to tubular damage by its own as demonstrated by positive signal for HCV observed in the perinuclear area of tubular epithelial cells and infiltrating cells on immunohistochemistry and in situ hybridization. HCV is also strongly associated with glucose abnormalities, with a negative impact on renal function. HCV infection is itself an independent risk factor for CKD and end-stage renal disease. New direct antiviral agents (DAAs) can be used for HCV treatment with a sustained viral response (SVR) > 90%, but the effect of HCV clearance on kidney is still unknown.The aim of the study was to evaluate the effect of viral eradication on renal glomerular (GI) and tubular (TI) involvement in patients with HCV related cirrhosis.
Materials and Methods: 94 patients with HCV Child A cirrhosis treated with DAAs were enrolled. The diagnosis of liver cirrhosis was performed by liver biopsy and/or Transient Elastography. Estimated glomerular filtration rate (eGFR) estimated by CKD-EPI 2009 equation.Urinary albumin-to-creatinine ratio (ACR), urinary alpha1-microglobulin-to-creatinine ratio (a1MCR) and FeNa were evaluated before therapy (T0) and six months after treatment (FU6). Glomerular involvement was defined as ACR > 30 mg/g, tubular involvement as a1MCR > 14 mcg/mc and FeNa > 1.
Results: eGFR was > 90 ml/min/1,73m2 in 58/94 pts (61.7%), 60-89 ml/min/1.73m2 in 30/94 pts (31.9%) and 45-59 ml/min/1.73m2 in 6/94 pts (6.4%). 39 pts (41.5%) showed RI. GI was found in 19/39 pts (48%) and TI in 30/39 pts (76%), they co-occured in 10/39 pts (25%). Patients with renal involvement showed renal lower eGFR values than patients without renal involvement (95.2+-15.2 vs 85+-5.8, p=0.07). A significant reduction of ACR was demonstrated in patients with GI without diabetes (13 pts) 6 months after interferon free treatment compared to baseline (73.5 +- 138.5 mg/g vs 19.9 +- 12.3 mg/g, p=0.019). In diabetic patients ACR values did not change after treatment. GI resolved in 11/13 patients (84,6%) without diabetes compared to none of 6 patients with diabetes (p=0.001).
In patients with TI we found a significant reduction of a1MCR and FeNa at FU6 compared to baseline.
Conclusion: Our study confirms a strong relationship between HCV and either glomerular either tubular involvement which can be revert by antiviral treatment. In diabetic patients GI did not change after therapy, so it seems to be related to the metabolic disorder, rather than HCV infection itself. This is the first report that demonstrates an improvement of TI and GI in non diabetic patients 6 months after HCV eradication with direct antiviral agents, demonstrating the pathogenetic role of HCV in renal damage
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