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Hepatitis C virus and the kidney

Nature Reviews Nephrology volume 15, pages 73–86 (2019)Cite this article

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Abstract

Hepatitis C virus (HCV) infection is more prevalent and is associated with higher mortality in patients receiving dialysis and in kidney transplant recipients than in the general population. Kidney transplant recipients who are HCV-positive are also at higher risk of allograft and liver failure than are HCV-negative recipients. Moreover, HCV infection is associated with a higher incidence and faster progression of diabetes mellitus and chronic kidney disease (CKD), as well as a higher incidence of systemic (especially cardiovascular) complications. The finding that these complications of HCV infection are attenuated in patients who achieve a sustained virologic response (SVR) emphasizes the need to treat patients with CKD who are HCV-positive with oral antiviral therapies. Fortunately, the available evidence suggests that a SVR can be achieved in >95% of patients with late-stage CKD and in kidney transplant recipients. According to international guidelines, all patients with CKD and HCV infection should be considered for treatment with direct acting antivirals (DAAs), prioritizing those with symptomatic cryoglobulinaemic vasculitis, extensive liver fibrosis and stage 4–5 CKD. DAA treatment can be delayed until after transplantation in recipients whose waiting time is markedly reduced by accepting an HCV-positive organ. An emerging issue is the long-term renal safety of DAAs, which requires a re-appraisal. Overall, the elimination of HCV from patients with CKD now seems to be achievable, provided that DAA treatment is coupled with reinforced hygienic precautions to prevent reinfections in dialysis units.

Key points

  • Hepatitis C virus (HCV) infection is more frequent in patients with chronic kidney disease (CKD) than in the general population; it is associated with a high risk of hepatic and extra-hepatic complications, including rapid CKD progression.

  • Patients with CKD and HCV infection should be considered for treatment with direct acting antivirals (DAAs).

  • Current DAA regimens lead to a sustained virologic response (SVR) in over 95% of patients with severe CKD.

  • Achieving a SVR decreases the risk of both hepatic and extra-hepatic complications; understanding the long-term effects of DAAs on kidney function requires additional follow-up studies.

  • Use of HCV-positive organs in HCV-negative kidney transplant candidates could reduce the waiting time for transplantation; HCV infection should then be treated after kidney transplantation.

  • Coupling antiviral treatment with reinforced hygienic precautions to prevent reinfections, especially in haemodialysis units, has the potential to eliminate HCV infection from the nephrology field.

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Fig. 1: HCV infection is a systemic disease.
Fig. 2: Mechanisms of kidney damage following HCV infection.
Fig. 3: The HCV replication cycle and sites of action of direct acting antivirals.
Fig. 4: History of antiviral therapies for HCV infection.
Fig. 5: Therapeutic options for treating hepatitis C virus infection.

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Reviewer information

Nature Reviews Nephrology thanks L. Rostaing, M. Sise and the other, anonymous reviewer(s) for their contribution to the peer review of this work.

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Authors and Affiliations

  1. Université Paris Descartes; Hepatology Department, Cochin Hospital, APHP; INSERM U1223, UMS-20 and Center for Translational Science, Institut Pasteur, Paris, France

    Stanislas Pol & Lucia Parlati

  2. Department of Nephrology, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium

    Michel Jadoul

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  1. Stanislas Pol
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All authors contributed equally to researching data for the article, discussions of the article’s content, writing the article, and review and/or editing of the manuscript before submission.

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Correspondence to Stanislas Pol.

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Competing interests

S.P. has acted as a speaker or board member for Bristol-Myers Squibb, Boehringer Ingelheim, Janssen, Gilead, Roche, MSD and Abbvie, and has received grants from Bristol-Myers Squibb, Gilead, Roche, Abbvie and MSD. M.J. has acted as a speaker for MSD and Abbvie, and as a Board Member for MSD. He has also received a grant from MSD. He co-chaired the 2018 update of the HCV and CKD KDIGO Guideline and is co-chair elect of KDIGO. L.P. declares no competing interests.

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Glossary

Variceal haemorrhage

Haematemesis or melena caused by esophageal or gastric varices rupture due to portal hypertension (associated with cirrhosis or non-cirrhotic portal hypertension).

Ascites

Transudate abdominal effusion caused by the combination of portal hypertension and liver failure (hypoalbuminaemia) in cirrhosis.

Cryoglobulinaemia

The presence of proteins (mostly immunoglobulins) that precipitate and become insoluble at low temperatures (<37 °C).

Non-Hodgkin lymphoma

A group of blood cancers that develop in lymphocytes and include all types of lymphoma except Hodgkin lymphoma. Risk factors for developing non-Hodgkin lymphoma include hepatitis C virus infection, Epstein Barr virus infection, Helicobacter pylori infection and autoimmune disease.

Sustained virologic response

(SVR). Defined by undetectable levels of hepatitis C virus RNA in the serum 12 or 24 weeks after the end of antiviral treatment and corresponds to virologic cure.

Complement

A component of the innate immune system that promotes phagocytosis through opsonization of antigens and inflammation through the attraction of macrophages and neutrophils and the destruction of pathogenic cell membranes.

Fibrinoid necrosis

A form of necrosis that is characterized by the accumulation of a proteinaceous material in the matrix in response to an inflammatory stimulus. It is typical of immune vasculitis.

Cryoglobulins

Proteins (mostly immunoglobulins) that precipitate and become insoluble at low temperatures (<37 °C)

Crescents

Histological manifestations of glomerulonephritis that are caused by the proliferation of parietal epithelial cells lining the Bowman capsule in response to an inflammatory stimulus.

Tubular casts

The result of the intraluminal precipitation of Tamm–Horsfall mucoproteins, which are secreted by renal tubular cells. Cast formation is favoured by low flow, concentrated salts and low pH.

Enzyme immunoassay

(EIA). A biochemical test that measures the presence and/or concentration of a protein or enzyme in a solution (serum or urine) through the use of a specific antibody.

Ritonavir boost

Ritonavir is an efficient anti-HIV agent but is toxic at therapeutic doses. It is now used as a ‘booster’, to enhance the efficacy of protease inhibitors, thereby enabling the use of lower doses and reducing their putative toxicity.

Second-generation DAAs

Direct-acting antivirals (DAAs) available from 2013, including sofosbuvir, simeprevir, daclatasvir, ledipasvir, paritaprevir, ritonavir, ombitasvir, dasabuvir, elbasvir and grazoprevir.

Pangenotypic

Refers to direct-acting antivirals with established efficacy regardless of the hepatitis C virus genotype.

Decompensated cirrhosis

Refers to cirrhosis with ascites, variceal bleeding or hepatic encephalopathy.

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Pol, S., Parlati, L. & Jadoul, M. Hepatitis C virus and the kidney. Nat Rev Nephrol 15, 73–86 (2019). https://doi.org/10.1038/s41581-018-0081-8

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