Abstract and Introduction
Objectives: To study the pathologic spectrum of kidney diseases in patients with hepatitis C virus infection (HCV+).
Methods: Native kidney biopsy specimens in HCV+ patients were reviewed.
Results: A total of 9,836 native kidney biopsy specimens were evaluated from January 2007 to December 2016, of which 273 (2.8%) were from HCV+ patients, and of these, 115 (42.1%) had diagnoses consistent with HCV-associated glomerulonephritis (GN). Non–HCV-associated kidney diseases comprised most diagnoses (158 cases, 57.9%) including non–immune complex–mediated kidney diseases (127 cases, 46.5%) and other immune complex–mediated glomerular diseases (31 cases, 11.4%). Forty-one (40.6%) patients had HCV-associated GN among 101 HCV+ patients from 2007 to 2011 vs 74 (43.0%) patients with HCV-associated GN among 172 HCV+ patients from 2012 to 2016. HCV-associated GN showed five morphologic patterns: focal proliferative (5.2%), diffuse mesangial proliferative (50.4%), diffuse membranoproliferative (28.7%), proliferative GN with crescentic lesions (7.8%), and membranous patterns (7.8%).
Conclusions: We found a spectrum of pathologic changes in renal biopsy specimens of HCV+ patients, with most having diseases unrelated to HCV infection, HCV-associated GN showing five morphologic patterns, and availability of effective HCV antiviral therapy not yet resulting in major changes in the spectrum of kidney diseases in these patients.
Hepatitis C virus (HCV) is an RNA virus that was discovered in 1989 during the search for the cause of non-A, non-B hepatitis. HCV infection is estimated to be present in 2.8% of the world population and 1.3% of the North American population. Extrahepatic manifestations associated with HCV infection have been studied since the early 1990s,[2,3] when the association of HCV infection with mixed cryoglobulinemia and kidney disease was recognized.[4,5] Kidney disease in patients with HCV infection has been reported most frequently to be membranoproliferative glomerulonephritis (MPGN), but other patterns of glomerulonephritis (GN), including mesangial proliferative GN, membranous GN, fibrillary GN, and immunotactoid glomerulopathy, are also reported.[9,10] The exact relationship between HCV infection and renal disease remains to be completely settled, especially in those patients without cryoglobulinemia. A meta-analysis showed absence of a relationship between HCV seropositive status and reduced estimated glomerular filtration rate, although HCV seropositive serology was an independent risk factor for proteinuria in the general population.
Until a few years ago, there were only two drugs for HCV treatment: pegylated-interferon and ribavirin.[12–14] Since April 2011, direct-acting antiviral agents (DAAs) have been approved for HCV treatment, and they have achieved great success with high sustained virologic response.[15–17] Some reports showed a decrease or clearance of cryoglobulinemia after direct antiviral treatment, while others showed persistence of cryoglobulinemia after HCV eradication.[18–20] There are even reports of cases of new-onset HCV-associated GN following sustained virologic response with DAA therapy. Therefore, it is unclear whether this dramatic improvement of HCV treatment has resulted in a change in the spectrum of HCV-associated kidney diseases in those HCV+ patients or not. The objectives of this study were to characterize the native kidney biopsy specimens in patients with HCV infection in a 10-year period and to compare the spectrum of kidney diseases in these patients seen in the pre-DAA (2007–2011) and post-DAA (2012–2016) eras.
Am J Clin Pathol. 2021;156(3):399-408. © 2021 American Society for Clinical Pathology