Spectrum of Kidney Diseases in Patients With Hepatitis C Virus Infection

A 10-Year Study

Shunhua Guo, MD; Meghan E. Kapp, MD; Diego M. Beltran, MD; Cesar Y. Cardona, MD; Dawn J. Caster, MD; Ronald R. Reichel, MD; Agnes B. Fogo, MD


Am J Clin Pathol. 2021;156(3):399-408. 

In This Article

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.[1] 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,[6] membranous GN,[7] fibrillary GN, and immunotactoid glomerulopathy,[8] 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.[11]

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.[21] 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.