Guidelines for Hepatitis C in Chronic Kidney Disease Issued

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Guidelines for Hepatitis C in Chronic Kidney Disease Issued

News Author: Laurie Barclay, MD
CME Author: Laurie Barclay, MD
Disclosures
Release Date: April 8, 2008

From National Kidney Foundation (NFK) 2008 Spring Clinical Meetings

April 7, 2008 — The first global clinical practice guidelines for patients with chronic kidney disease (CKD) were presented on April 4 at the National Kidney Foundation 2008 Spring Clinical Meetings in Dallas, Texas, and published as a supplement to the April 2008 issue of Kidney International. These guidelines, developed by the Kidney Diseases Improving Global Outcomes (KDIGO) foundation, address the prevention, management, and treatment of hepatitis C virus (HCV) infection in patients with CKD and patients in hemodialysis units.

"The KDIGO guidelines are the first global guidelines in nephrology," guidelines authors Michel Jadoul, MD, head of nephrology, Cliniques Universitaires Saint Luc, Université Catholique de Louvain in Brussels, Belgium, tells Medscape Nephrology. "Hepatitis C was identified by the KDIGO board of Directors as a good topic for the first global guidelines in nephrology, relevant for both developed and developing countries. Hepatitis C is both a cause and consequence of CKD, and [there are] multiple opportunities for improving the care of CKD patients in this field, e.g. by reducing transmission to hemodialysis patients, especially in developing countries."

Infection with HCV is more common in patients with CKD vs the general population. The new guidelines are intended to be globally applicable in a variety of clinical settings, particularly nephrology and transplant practices.

"HCV infection is a major worldwide public health problem with an estimated 170 million affected individuals globally, and 3.2 million Americans chronically infected with the virus," Bertrand L. Jaber, MD, MS, FASN, and an associate professor of medicine at Tufts University School of Medicine in Boston, Massachusetts, tells Medscape. He was not involved with writing these guidelines but was asked to provide independent commentary.

"HCV infection is associated with an increased prevalence of reduced kidney function, albuminuria, and an increased risk of developing end stage renal disease," says Dr. Jaber, who is also vice chair for clinical affairs, Department of Medicine at Caritas St. Elizabeth's Medical Center, "HCV infection is also associated with increased mortality among patients undergoing maintenance hemodialysis and among kidney transplant recipients."

To detect HCV infection and to prevent transmission, the guidelines strongly urge testing for HCV in patients receiving maintenance hemodialysis and in those who are candidates for kidney transplantation. Testing of all kidney donors for HCV is also recommended, as are infection-control procedures including hygienic precautions that effectively prevent transfer of contaminated blood or fluids.

"The guidelines should help improve a lot the currently suboptimal prevention of hepatitis C transmission in many hemodialysis units worldwide, which is currently mainly nosocomial," Dr. Jadoul says. "The literature review highlighted substantial evidence that preventative strategies should concentrate on basic hygienic precautions, rather than strategies currently popular in many countries such as in Europe, Asia, etc. In addition, a detailed evidence-based review of the literature is now available as guidance for all nephrologists, virologists, hepatologists, hemodialysis nurses, and transplant physicians not necessarily familiar with the specifics of hepatitis C in CKD patients."

Along with David Roth, MD, from Miami, Florida, Dr. Jadoul led an international, multidisciplinary team of 14 experts in nephrology, virology, hepatology, transplantation, and infectious diseases. The resulting evidence-based Clinical Practice Guidelines address diagnosis and evaluation of HCV infection in patients with CKD, treatment of HCV infection in this population, prevention of HCV transmission in hemodialysis units, management of HCV-infected patients before and after renal transplant, and diagnosis and management of renal diseases associated with HCV infection.

"The guideline covers aspects of the diagnosis and treatment of hepatitis C relevant to nephrologists across the world," David Wheeler, MD, FRCP, a reader in Nephrology at Royal Free and University College London, United Kingdom, told Medscape Nephrology when asked to provide additional independent review of these guidelines. "To my knowledge, there has not been a previous document published with this remit. The guidelines will increase awareness of the importance of hepatitis C infection as a potentially treatable cause of chronic kidney disease worldwide [and are] likely to help to unify the management of kidney disease in hepatitis C-infected patients."

To develop these recommendations, the expert panel used an evidence based approach modeled on that used by the NKF-Kidney Disease Outcome Quality Initiative (KDOQI), with a particular focus on reconciling these guidelines with other US-based guidelines on HCV.

"The development of evidence-based clinical practice guidelines for the prevention, diagnosis, evaluation, and treatment of HCV infection in patients with CKD is of extreme value for healthcare providers," Dr. Jaber says. "The KDOQI panel considered the medical delivery system in the US, including costs and reimbursement-related issues, and summarized key guidelines for the diagnosis, evaluation, and management of HCV infection in patients with CKD."

An independent work group and 3 methodology centers located in different parts of the world rigorously reviewed available evidence in the literature and formulated draft practice guidelines, which then underwent a 3-tier review process including internal review by the KDIGO Board; organizational review by leading patient groups; medical societies; and government agencies; and, finally, open peer review. Wherever appropriate, reviewer comments were included in the finalized guidelines published in Kidney International.

"All relevant aspects are covered from diagnosis to management and treatment, in addition to prevention," Dr. Jadoul says. "The next step after publication is of course dissemination and then implementation. . . with advantage taken of all relevant meetings of health specialists to maximize the benefits of optimal implementation."

The key recommendations in these guidelines have already been translated into 4 languages, according to Dr. Wheeler. In the weeks to come, the guideline statements will be translated into several major global languages, including Arabic, French, German, Italian, Russian, Turkish, Chinese, Japanese, and Spanish.

"Earlier screening for kidney disease among patients infected with HCV is likely to result in earlier detection of chronic kidney disease and, ideally, help reduce the burden of progressive kidney disease," Dr. Jaber explains. "However, research studies are still needed to determine the optimal timing of screening for CKD in HCV-infected patients, the frequency of testing, and the cost-benefit relationship of this approach."

Although Dr. Wheeler anticipates that the guidelines will be widely used, he notes that the main barriers to implementation are likely to be the cost of testing for and treating HCV infection.

"As some misunderstandings are still common and changes of human behavior are usually relatively slow, years will be required for widespread implementation (true for any guideline!), but the potential benefit is enormous," Dr. Jadoul concludes. "Let us only consider prevention: in some countries, up to 3-10% of hemodialysis patients become infected by hepatitis C each year! The guidelines will undoubtedly also help standardize or optimize several aspects of the care to hepatitis C CKD patients, including pre-kidney transplant evaluation."

Dr. Jadoul's unit has received research grants and support from Amgen. Dr. Jaber has disclosed no relevant financial relationships. Dr. Wheeler has received honoraria and research funding from Roche Pharmaceuticals. The complete list of disclosures is available in the original article.

National Kidney Foundation 2008 Spring Clinical Meetings: Session 285. April 2–6, 2008.

Kidney Intl. 2008;73(suppl 109):S1-S99.
Study Highlights

    * Using a rigorous process including literature review and multidisciplinary team input, KDIGO developed evidence-based Clinical Practice Guidelines.
    * These are the first global guidelines developed for patients with CKD.
    * Translation of the guidelines into numerous languages and presentation at appropriate meetings should promote widespread implementation.
    * These guidelines address diagnosis, evaluation, and treatment of HCV infection in patients with CKD; prevention of HCV transmission in hemodialysis units; management of HCV-infected patients before and after renal transplant; and diagnosis and management of renal diseases associated with HCV infection.
    * For the detection of HCV infection and the prevention of transmission, patients receiving maintenance hemodialysis, those who are candidates for kidney transplantation, and all kidney donors should be tested for HCV.
    * Patients undergoing hemodialysis should be tested for HCV when they first start hemodialysis or when they transfer from another hemodialysis facility.
    * In hemodialysis units with low prevalence of HCV, initial testing should be enzyme immunoassay (EIA), followed by nucleic acid testing (NAT) if positive.
    * Hemodialysis units with high prevalence of HCV should do initial testing with NAT.
    * Patients undergoing hemodialysis who test negative for HCV may be retested every 6 to 12 months with EIA.
    * Patients undergoing hemodialysis with unexplained abnormal aminotransferase levels should be tested for HCV with NAT.
    * If a new HCV infection in a hemodialysis unit is suspected to be nosocomial, all patients who may have been exposed should be tested with NAT.
    * Patients who are initially NAT negative should have repeated testing with NAT within 2 to 12 weeks.
    * Infection-control procedures should include hygienic precautions that effectively prevent transfer of contaminated blood or fluids.
    * The decision to treat patients with CKD and HCV infection should be based on the potential benefits and risks for therapy, including life expectancy, candidacy for kidney transplantation, and comorbidities.
    * In patients with CKD (except for kidney transplant recipients) in whom acute HCV infection develops, a waiting period of more than 12 weeks to observe spontaneous clearance (by NAT) is not justified, and antiviral treatment should be started.
    * HCV-infected patients accepted for kidney transplantation should be treated.
    * Treatment of HCV-infected kidney transplant recipients should be considered only when the benefits of treatment clearly outweigh the risk for allograft rejection from interferon (IFN)-based therapy (eg, fibrosing cholestatic hepatitis, life-threatening vasculitis).
    * Antiviral therapy should be considered for patients with HCV-related glomerulonephritis.
    * As in the general population, HCV-infected patients with CKD stages I and II should receive combined antiviral treatment with use of pegylated IFN and ribavirin, with ribavirin dose titrated based on patient tolerance.
    * HCV-infected patients with CKD stages III, IV, and V not yet undergoing dialysis should receive monotherapy with pegylated IFN, with doses adjusted to the level of kidney function.
    * HCV-infected patients with CKD stage VD undergoing maintenance hemodialysis should receive monotherapy with standard IFN that is dose adjusted for a glomerular filtration rate (GFR) of less than 15 mL/minute/1.73 m2.

Pearls for Practice

    * For the detection of HCV infection and the prevention of transmission, patients receiving maintenance hemodialysis, those who are candidates for kidney transplantation, and all kidney donors should be tested for HCV.
    * As in the general population, HCV-infected patients with CKD stages I and II should receive combined antiviral treatment with use of pegylated IFN and ribavirin. HCV-infected patients with CKD stages III, IV, and V not yet undergoing dialysis should receive monotherapy with pegylated IFN. HCV-infected patients with CKD stage VD undergoing maintenance hemodialysis should receive monotherapy with standard IFN that is dose adjusted for a GFR of less than 5 mL/minute/1.73m2.

http://www.medscape.com/viewarticle/572657