Evaluation and Treatment of Hepatitis C in Patients with Chronic Kidney Disease Not on Dialysis

 

This reference tool highlights select guidelines adapted from the KDIGO Clinical Practice Guidelines for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease for implementation in the United States and in accordance with the KDOQI U.S. Commentary.

Adapted from the KDIGO Clinical Practice Guidelines for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease.

And the KDOQI U.S. commentary on the KDIGO Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation and Treatment of Hepatitis C in CKD.

Highlights select guidelines.
To view the full Guideline document, visit www.kdigo.org

THE NATURAL HISTORY OF HEPATITIS C IN THE GENERAL POPULATION

HCC=Hepatocellular carcinoma
HIV=Human immunodeficiency virus

Note: Little is known about the natural history of HCV infection in the CKD population, or if it differs substantially from the general population with normal kidney function.

GROUPS AT RISK FOR HEPATITIS C


** Other= Hemodialysis patients; health care workers; perinatal transmission

EVALUATION

GUIDELINE 1.1.1
It is suggested that CKD patients be tested for HCV (weak evidence). Finding HCV gives the chance to offer antiviral treatment to those who could benefit from it.

G 2.1.1
It is suggested that CKD patients with HCV infection be evaluated for antiviral treatment. (Weak)

G 2.1.2
It is suggested that the decision to treat be based on the potential benefits and risks of therapy (Weak):

  • life expectancy
  • candidacy for kidney transplantation
  • comorbidities such as significant coronary artery disease

Applicability of Guideline 1 to the United States

HCV testing of patients with CKD should be performed in patients with unexplained proteinuria, microscopic hematuria, increased aminiotransferase levels and risk factors for HCV acquisition..

Potential benefits:

  • Sustained virologic response (SVR) and slowed progression of liver disease and HCV-mortality. (In the general population, achieving SVR may improve survival and lower the rate of hepatocellular carcinoma. No data exist to indicate that achieving SVR translates into improved survival in the CKD population infected with HCV.)
  • Theoretically lowered all-cause mortality rate. (In the general population, the 5-year mortality rate of HCV-infected patients with compensated cirrhosis is 9%.) In the absence of HCV, the CKD patient has a high mortality rate.

G 2.1.3
It is suggested that in CKD patients-except kidney transplant recipients-who develop an acute HCV infection, a waiting period beyond 12 weeks to observe spontaneous clearance (by NAT) is not justified and that antiviral treatment should be started. (Weak)

G 2.1.6
It is suggested that antiviral therapy be considered for patients with HCV-related GN (see Guideline 5.3). (Weak)

COUNSEL PATIENT: Discuss potential side effects and the likelihood of a beneficial treatment outcome.

CONTRAINDICATIONS to combined Interferon (IFN) and ribavirin therapy:

Absolute contraindication in patients who are pregnant or breastfeeding. Relative contraindications:

  • Major, uncontrolled depressive illness
  • Ongoing, untreated substance abuse or alcohol abuse
  • Concurrent cardiac or neuropsychiatric illness
  • Patients >60 years of age are in a higher risk group for the development of serious adverse reactions to IFN and require individual decision-making.
  • Poorly controlled diabetes
  • Obstructive pulmonary disease

COUNSEL PATIENT: Discuss potential side effects and the likelihood of a beneficial treatment outcome.

TREATMENT (GUIDELINE 2.2)

Treatment in patients with CKD should be individualized, with doses adjusted to the level of kidney function.

TREATMENT: CKD STAGES 1 and 2

As in the general population, HCV-infected patients with CKD stages 1 and 2 should receive combined antiviral treatment with use of pegylated interferon (peg IFN ) and ribavirin.

Minimally impaired kidney function (>50ml per min per 1.73 m2) does not have a major impact on the efficacy and safety of combined IFN and ribavirin therapy.

ADJUST DOSE FOR PATIENT TOLERANCE

TREATMENT: CKD STAGES 3-5, Not on Dialysis

Recommended treatment of HCV infection in patients with CKD and their associated adverse effects.

Stage of CKD Events        IFN       Ribavirin        Common Adverse

STAGE 3 (GFR >50)

Use combined interferon and ribavirin (as in stages 1 and 2), if it is tolerated and GFR is above 50.

Ribavirin is not appropriate if eGFR is below 50 because of hemolytic anemia; monotherapy with pegylated IFN is the treatment of choice.

STAGE 3 (GFR <50)

Monotherapy with pegylated INF is recommended.

The use of ribavirin in patients with a GFR < 50 mL per min per 1.73 m2 is not recommended.

CAUTION: At lower levels of kidney function in the CKD population, the pharmacokinetics of antiviral drugs targeted at HCV is affected: Beware of reduced clearance of Peg- IFN and ribavirin.

STAGES 4 and 5, Not on Dialysis*

Treat with pegylated IFN, with doses adjusted to GFR level.

CLEARANCE CONSIDERATIONS
Clearance of IFN in patients with CKD Stages 3 and 4 may be reduced and may require dose adjustment.

Clearance of ribavirin can be significantly reduced even in patients with GFR >50. Measure ribavirin levels often.

Estimated GFR is a significantly better predictor of ribavirin clearance than body weight alone.

Applicability of Guideline 2 to the United States

Although the available evidence supporting HCV treatment is weak as applied to the U.S. population, it favors treatment of appropriate individuals. Thus, after weighing the risks and benefits for the individual patient, treatment is indicated because of the high morbidity and mortality associated with persistent HCV infection. Specifically, patients with CKD stages 1 to 2 are candidates for the current gold standard of PEG-IFN and ribavirin, and HD patients appear to have high SVR rates after IFN monotherapy. Further study is needed to clarify the overall clinical benefit of HCV treatment in U.S. patients with CKD and the optimal treatment strategy for patients with all stages of CKD.

ASSESS TREATMENT RESPONSE

G2.3.1 SVR, defined as HCV RNA clearance 6 months after completion of antiviral treatment, is suggested for assessing response to antiviral treatment. (Weak)

2.3.2 If SVR is achieved, it is suggested that testing with NAT be performed annually to ensure that the patient remains nonviremic. (Weak)

Sustained HCV RNA clearance of viremia at 6 months after discontinuing treatment remains the gold standard to evaluate the efficacy of antiviral therapy in patients with hepatitis C and normal kidney function.

G2.3.3 All patients with HCV infection, regardless of treatment or treatment response, should be followed for HCV-associated comorbidities. (Strong)

  • Patients who have evidence of clinical or histologic cirrhosis should have follow-up every 6 months.(Strong)
  • Annual follow-up for patients without cirrhosis is suggested. (Weak)

MONITOR FOR HCV-ASSOCIATED COMORBIDITIES (GUIDELINE 2.3.3)

All patients with HCV infection, regardless of treatment or treatment response, should be followed for potential HCV-associated comorbidities.

Hepatic HCV effects

Nonhepatic HCV effects

  • hepatic fibrosis/cirrhosis
  • hepatocellular carcinoma
  • end stage liver disease
  • Coinfection with HIV or HBV
  • Lymphoproliferative disorders
  • Mixed cryoglobulinemia
  • Lymphoma
  • Dermatopathologic manifestations
  • Neurologic disorders including encephalopathy
  • Disorders of the joints, bones and muscles
  • Endocrinologic disorders
  • Lung and cardiocirculatory disorders
  • Psychopathological disorders

GLOBAL PREVALENCE
OF HEPATITIS C
 
a

The World Health Organization (WHO) estimates that about 170 million people, 3% of the world's population, are infected with HCV.

(Source: WHO Fact Sheet WHO/164 - October 2000.)

Hepatitis C estimated prevalence and number infected by WHO Region:

WHO Region

Hepatitis C prevalence
Rate %

Infected Population
(Millions)

Africa

5.3

31.9

Americas

1.7

13.1

Eastern Mediterranean

4.6

21.3

Europe

1.03

8.9

South-East Asia

2.15

32.3

Western Pacific

3.9

62.2

Total

3.1 %

169.7

 

REFERENCES


  1. KDOQI US commentary on the KDIGO clinical practice guideline for the prevention, diagnosis, evaluation and treatment of Hepatitis C in CKD. Kidney International. 2008; in press.
  2. Strader DB, Wright T, Thomas DL, Seeff LB. Diagnosis, management and treatment of Hepatitis C. AASLD Practice Guideline. Available at: www.aasld.org. Accessed 09/17/08.
  3. Centers for Disease Conrol and Prevention. A comprehensive strategy for the prevention and control of Hepatitis C Virus Infection and its consequences. Available at: www.cdc.gov/hepatitis/HCV/Strategy/NatHepCPrevStrategy.htm. Accessed 9/17/08.

SECTION I: USE OF THE CLINICAL PRACTICE GUIDELINES
These Clinical Practice Guidelines are based on the best information available at the time of publication. They are designed to provide information and assist decision-making. They are not intended to define a standard of care and should not be construed as one, nor should they be interpreted as prescribing an exclusive course of management.

Variations in practice will inevitably and appropriately occur when clinicians take into account the needs of individual patients, available resources and limitations unique to an institution or a type of practice. Every health care professional making use of these guidelines is responsible for evaluating the appropriateness of applying them in the setting of any particular clinical situation. The recommendations for research contained within this document are general and do not imply a specific protocol.

SECTION II: Disclosure
Kidney Disease Outcomes Quality Initiative (KDOQI) makes every effort to avoid any actual or reasonably perceived conflicts of interest that may arise as a result of an outside relationship or a personal, professional or business interest of a member of the Work Group.

Specifically, all members of the Work Group are required to complete, sign and submit a disclosure and attestation form showing all such relationships that might be perceived as actual or perceived conflicts of interest. This document is updated annually and information is adjusted accordingly. All reported information is on file at the National Kidney Foundation.