HCV cirrhotic patients treated with direct-acting antivirals: Detection of tubular dysfunction and resolution after viral clearance

Elisa Biliotti; Donatella Palazzo; Francesca Tinti; Maria Domenica D'Alessandro; Rozenn Esvan; Raffaella Labriola; Andrea Cappoli; Ilaria Umbro; Lorenzo Volpicelli; Alessandra Bachetoni; Erica Villa; Anna Paola Mitterhofer; Paola Rucci; Gloria Taliani

doi:10.1111/liv.14672

HCV cirrhotic patients treated with direct-acting antivirals: Detection of tubular dysfunction and resolution after viral clearance

Liver Int. 2021 Jan;41(1):158-167. doi: 10.1111/liv.14672.

Affiliations

¹ Hepatology Unit, Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy.
² Nephrology Unit, Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy.
³ Clinical Pathology, Department of Experimental Medicine, Sapienza University, Rome, Italy.
⁴ Division of Gastroenterology, Azienda Ospedaliero-Universitaria Policlinico di Modena, University of Modena and Reggio Emilia, Modena, Italy.
⁵ Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy.

PMID: 32979012
DOI: 10.1111/liv.14672

Abstract

Background/aims: Hepatitis C virus (HCV) has been identified in tubular epithelial cells of infected patients; however, the presence of tubular dysfunction, which is a risk factor for chronic kidney disease (CKD), has never been examined in vivo. The present prospective longitudinal study aimed to estimate the prevalence of tubular dysfunction alone or with glomerular damage and its evolution after HCV clearance in cirrhotic patients.

Methods: One hundred and thirty-five consecutive Child-Pugh A cirrhotic patients were evaluated before antiviral treatment and 6 months after the end of therapy. Tubular dysfunction was evaluated by urinary alpha1-microglobulin to creatinine ratio (α1-MCR), and glomerular damage was assessed by urinary albumin to creatinine ratio (ACR).

Results: Almost all the patients (93.3%) showed a normal or mildly decreased e-GFR (KDIGO-G1/G2-categories). Tubular dysfunction was found in 23.7% (32/135) of patients, co-occurring with glomerular damage in 37.5% (12/32) of cases, while glomerular damage was found in 16.3% (22/135) of patients. In multiple logistic regression, glomerular damage and the concomitant presence of diabetes and hypertension were the only predictors significantly associated with tubular dysfunction. After HCV clearance, patients experienced a significant reduction of α1-MCR levels (21.0 vs 10.5 μg/mg, P = .009) and tubular dysfunction resolved in 57.1% of subjects.

Conclusions: Tubular dysfunction is an unrecognized feature of HCV-related kidney disease in cirrhotic patients and its presence should be primarily investigated in subjects with glomerular damage, diabetes and hypertension, despite normal e-GFR. Tubular dysfunction resolves in the majority of cases after HCV clearance; however, it may persist after antiviral treatment and further studies should evaluate its long-term impact on kidney function.

Keywords: chronic hepatitis C; compensated cirrhosis; direct-acting antiviral agents (DAAs); glomerular damage; proximal tubular dysfunction.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antiviral Agents / therapeutic use
Hepacivirus
Hepatitis C* / complications
Hepatitis C* / drug therapy
Hepatitis C* / epidemiology
Hepatitis C, Chronic* / complications
Hepatitis C, Chronic* / drug therapy
Humans
Liver Cirrhosis / drug therapy
Liver Cirrhosis / epidemiology
Longitudinal Studies
Prospective Studies
Sustained Virologic Response

Substances

Antiviral Agents