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Oh what a tangled web it weaves, this virus called hepatitis C. HCV has evolved over several thousand years into seven genotypes and multiple subtypes, making identification and treatment extremely variable.1 The genotypes are usually geographically specific, with 70% to 75% of HCV patients in the United States classed as genotype 1.2 Genotypes 2 and 3 account for most of the rest.3
While genotype does not impact the course or severity of the disease, it does affect the response to treatment. With today’s newest treatments, success rates for sustained viral response (SVR) are as high as 90% in patients with genotype 1. However, the treatment is not without cost: About $100,000 for patients without cirrhosis and even more for those with it, due to the extended length of treatment.
Chronic kidney disease (CKD) and HCV overlap in 10% to nearly 59% of the population in some geographic areas.4 Those with CKD who have had a previous kidney transplant, been on dialysis, and/or been treated prior to the introduction of epoetin alfa (Epogen®, when blood transfusions were common) are more likely to be HCV-positive.
Unfortunately, patients often convert to HCV while on hemodialysis.4 This largely represents a nosocomial infection related to parenteral exposure. In the dialysis patient, the course of HCV is more aggressive than in others, with high morbidity—often resulting from cirrhosis and/or hepatocellular carcinoma.
With new HCV drugs available, CKD patients would appear to be a prime population to treat. In order to gain marketing approval, the FDA requires testing of new drugs in patients with varying degrees of renal impairment. However, the requirement is for “moderate” CKD, defined by the FDA as a glomerular filtration rate (GFR) of at least 30 mL/min/1.73m2. The FDA does not require testing for patients with a lower GFR, or what nephrology practices refer to as stage 4 or stage 5 CKD; thus, no data are available for this population. The available pharmacokinetic data for the recently approved regimens of sofosbuvir/ledipasvir (Harvoni®) and of ombitasvir/paritaprevir/ritonavir with dasabuvir (Viekira Pak™) suggest that no dosing modifications are necessary in the moderately impaired kidney population.
Continue for the newest HCV drugs >>
The recent approvals of Harvoni and Viekira Pak are considered game-changers in the treatment of chronic HCV infection: They demonstrate that interferon is no longer always necessary. Interferon, especially in combination with ribavirin, was especially toxic for patients in the kidney failure population, although the pegylated form of interferon was less problematic. FDA approvals for Harvoni and Viekira Pak were based on clinical data demonstrating SVR rates exceeding 90%, even in traditionally difficult-to-treat populations (ie, patients with genotype 1, African-Americans, those with high viral load levels), which include many CKD patients.
The lack of clinical data in the CKD stage 4/5 population at the time of drug approval raises significant management challenges for the HCV-positive CKD patient. It is encouraging, however, that the FDA is requiring that all new medications be tested in the renally impaired population, even if not in the severely impaired groups. In the interim, and based solely on renal impairment study results for patients with GFR at or exceeding 30 mL/min/1.73m2, HCV guidelines issued jointly by the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America5 include the recommendation that these new HCV medications be considered for use in the CKD population. Furthermore, there are no dosing adjustments recommended for any of the new HCV medications in stage 4 or stage 5 CKD due to lack of data. However, until more data become available, CKD patients must be managed on a case-by-case basis after consultation with a renal expert, with close attention to changes in GFR and adverse events.
When these new HCV medications are used in the general population and those with significant CKD, postmarketing reports to the FDA will be vital. Practitioners are encouraged to report adverse outcomes to the FDA MedWatch system (https://www.accessdata.fda.gov/scripts/medwatch). As any nephrology practice will tell you, we are starting to get phone calls from our hepatology colleagues asking for guidance, and the next few years will be a fascinating time for all of us. The promise of virologic cure for our HCV-positive patients is tangible and on the horizon.
REFERENCES
1. Maeterns G, Stuyyver L. Genotypes and genetic variation of hepatitis C cirus. Hep C Review. Dec 1998;ed 23.
2. Spach DH, Kim HN. Treatment of HCV genotype 1 (2015). www.hepatitisc.uw.edu/go/treatment-infection/treatment-genotype-1/core-concept/all. Accessed February 15, 2015.
3. Hepatitis C Technical Advisory Group. Hepatitis C genotypes and quasispecies (2005). www.hepatitis.va.gov/provider/reviews/genotypes.asp. Accessed February 15, 2015.
4. Carvalho-Filho RJ, Feldner AC, Silva AE, Ferraz ML. Management of hepatitis C in patients with chronic kidney disease. World J Gastroenterol. 2015;21(2):408-422.
5. American Association for the Study of Liver Diseases, Infectious Diseases Society of America. Recommendations for testing, managing, and treating hepatitis C. http://hcvguidelines.org. Accessed February 15, 2015.
Oh what a tangled web it weaves, this virus called hepatitis C. HCV has evolved over several thousand years into seven genotypes and multiple subtypes, making identification and treatment extremely variable.1 The genotypes are usually geographically specific, with 70% to 75% of HCV patients in the United States classed as genotype 1.2 Genotypes 2 and 3 account for most of the rest.3
While genotype does not impact the course or severity of the disease, it does affect the response to treatment. With today’s newest treatments, success rates for sustained viral response (SVR) are as high as 90% in patients with genotype 1. However, the treatment is not without cost: About $100,000 for patients without cirrhosis and even more for those with it, due to the extended length of treatment.
Chronic kidney disease (CKD) and HCV overlap in 10% to nearly 59% of the population in some geographic areas.4 Those with CKD who have had a previous kidney transplant, been on dialysis, and/or been treated prior to the introduction of epoetin alfa (Epogen®, when blood transfusions were common) are more likely to be HCV-positive.
Unfortunately, patients often convert to HCV while on hemodialysis.4 This largely represents a nosocomial infection related to parenteral exposure. In the dialysis patient, the course of HCV is more aggressive than in others, with high morbidity—often resulting from cirrhosis and/or hepatocellular carcinoma.
With new HCV drugs available, CKD patients would appear to be a prime population to treat. In order to gain marketing approval, the FDA requires testing of new drugs in patients with varying degrees of renal impairment. However, the requirement is for “moderate” CKD, defined by the FDA as a glomerular filtration rate (GFR) of at least 30 mL/min/1.73m2. The FDA does not require testing for patients with a lower GFR, or what nephrology practices refer to as stage 4 or stage 5 CKD; thus, no data are available for this population. The available pharmacokinetic data for the recently approved regimens of sofosbuvir/ledipasvir (Harvoni®) and of ombitasvir/paritaprevir/ritonavir with dasabuvir (Viekira Pak™) suggest that no dosing modifications are necessary in the moderately impaired kidney population.
Continue for the newest HCV drugs >>
The recent approvals of Harvoni and Viekira Pak are considered game-changers in the treatment of chronic HCV infection: They demonstrate that interferon is no longer always necessary. Interferon, especially in combination with ribavirin, was especially toxic for patients in the kidney failure population, although the pegylated form of interferon was less problematic. FDA approvals for Harvoni and Viekira Pak were based on clinical data demonstrating SVR rates exceeding 90%, even in traditionally difficult-to-treat populations (ie, patients with genotype 1, African-Americans, those with high viral load levels), which include many CKD patients.
The lack of clinical data in the CKD stage 4/5 population at the time of drug approval raises significant management challenges for the HCV-positive CKD patient. It is encouraging, however, that the FDA is requiring that all new medications be tested in the renally impaired population, even if not in the severely impaired groups. In the interim, and based solely on renal impairment study results for patients with GFR at or exceeding 30 mL/min/1.73m2, HCV guidelines issued jointly by the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America5 include the recommendation that these new HCV medications be considered for use in the CKD population. Furthermore, there are no dosing adjustments recommended for any of the new HCV medications in stage 4 or stage 5 CKD due to lack of data. However, until more data become available, CKD patients must be managed on a case-by-case basis after consultation with a renal expert, with close attention to changes in GFR and adverse events.
When these new HCV medications are used in the general population and those with significant CKD, postmarketing reports to the FDA will be vital. Practitioners are encouraged to report adverse outcomes to the FDA MedWatch system (https://www.accessdata.fda.gov/scripts/medwatch). As any nephrology practice will tell you, we are starting to get phone calls from our hepatology colleagues asking for guidance, and the next few years will be a fascinating time for all of us. The promise of virologic cure for our HCV-positive patients is tangible and on the horizon.
REFERENCES
1. Maeterns G, Stuyyver L. Genotypes and genetic variation of hepatitis C cirus. Hep C Review. Dec 1998;ed 23.
2. Spach DH, Kim HN. Treatment of HCV genotype 1 (2015). www.hepatitisc.uw.edu/go/treatment-infection/treatment-genotype-1/core-concept/all. Accessed February 15, 2015.
3. Hepatitis C Technical Advisory Group. Hepatitis C genotypes and quasispecies (2005). www.hepatitis.va.gov/provider/reviews/genotypes.asp. Accessed February 15, 2015.
4. Carvalho-Filho RJ, Feldner AC, Silva AE, Ferraz ML. Management of hepatitis C in patients with chronic kidney disease. World J Gastroenterol. 2015;21(2):408-422.
5. American Association for the Study of Liver Diseases, Infectious Diseases Society of America. Recommendations for testing, managing, and treating hepatitis C. http://hcvguidelines.org. Accessed February 15, 2015.
Oh what a tangled web it weaves, this virus called hepatitis C. HCV has evolved over several thousand years into seven genotypes and multiple subtypes, making identification and treatment extremely variable.1 The genotypes are usually geographically specific, with 70% to 75% of HCV patients in the United States classed as genotype 1.2 Genotypes 2 and 3 account for most of the rest.3
While genotype does not impact the course or severity of the disease, it does affect the response to treatment. With today’s newest treatments, success rates for sustained viral response (SVR) are as high as 90% in patients with genotype 1. However, the treatment is not without cost: About $100,000 for patients without cirrhosis and even more for those with it, due to the extended length of treatment.
Chronic kidney disease (CKD) and HCV overlap in 10% to nearly 59% of the population in some geographic areas.4 Those with CKD who have had a previous kidney transplant, been on dialysis, and/or been treated prior to the introduction of epoetin alfa (Epogen®, when blood transfusions were common) are more likely to be HCV-positive.
Unfortunately, patients often convert to HCV while on hemodialysis.4 This largely represents a nosocomial infection related to parenteral exposure. In the dialysis patient, the course of HCV is more aggressive than in others, with high morbidity—often resulting from cirrhosis and/or hepatocellular carcinoma.
With new HCV drugs available, CKD patients would appear to be a prime population to treat. In order to gain marketing approval, the FDA requires testing of new drugs in patients with varying degrees of renal impairment. However, the requirement is for “moderate” CKD, defined by the FDA as a glomerular filtration rate (GFR) of at least 30 mL/min/1.73m2. The FDA does not require testing for patients with a lower GFR, or what nephrology practices refer to as stage 4 or stage 5 CKD; thus, no data are available for this population. The available pharmacokinetic data for the recently approved regimens of sofosbuvir/ledipasvir (Harvoni®) and of ombitasvir/paritaprevir/ritonavir with dasabuvir (Viekira Pak™) suggest that no dosing modifications are necessary in the moderately impaired kidney population.
Continue for the newest HCV drugs >>
The recent approvals of Harvoni and Viekira Pak are considered game-changers in the treatment of chronic HCV infection: They demonstrate that interferon is no longer always necessary. Interferon, especially in combination with ribavirin, was especially toxic for patients in the kidney failure population, although the pegylated form of interferon was less problematic. FDA approvals for Harvoni and Viekira Pak were based on clinical data demonstrating SVR rates exceeding 90%, even in traditionally difficult-to-treat populations (ie, patients with genotype 1, African-Americans, those with high viral load levels), which include many CKD patients.
The lack of clinical data in the CKD stage 4/5 population at the time of drug approval raises significant management challenges for the HCV-positive CKD patient. It is encouraging, however, that the FDA is requiring that all new medications be tested in the renally impaired population, even if not in the severely impaired groups. In the interim, and based solely on renal impairment study results for patients with GFR at or exceeding 30 mL/min/1.73m2, HCV guidelines issued jointly by the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America5 include the recommendation that these new HCV medications be considered for use in the CKD population. Furthermore, there are no dosing adjustments recommended for any of the new HCV medications in stage 4 or stage 5 CKD due to lack of data. However, until more data become available, CKD patients must be managed on a case-by-case basis after consultation with a renal expert, with close attention to changes in GFR and adverse events.
When these new HCV medications are used in the general population and those with significant CKD, postmarketing reports to the FDA will be vital. Practitioners are encouraged to report adverse outcomes to the FDA MedWatch system (https://www.accessdata.fda.gov/scripts/medwatch). As any nephrology practice will tell you, we are starting to get phone calls from our hepatology colleagues asking for guidance, and the next few years will be a fascinating time for all of us. The promise of virologic cure for our HCV-positive patients is tangible and on the horizon.
REFERENCES
1. Maeterns G, Stuyyver L. Genotypes and genetic variation of hepatitis C cirus. Hep C Review. Dec 1998;ed 23.
2. Spach DH, Kim HN. Treatment of HCV genotype 1 (2015). www.hepatitisc.uw.edu/go/treatment-infection/treatment-genotype-1/core-concept/all. Accessed February 15, 2015.
3. Hepatitis C Technical Advisory Group. Hepatitis C genotypes and quasispecies (2005). www.hepatitis.va.gov/provider/reviews/genotypes.asp. Accessed February 15, 2015.
4. Carvalho-Filho RJ, Feldner AC, Silva AE, Ferraz ML. Management of hepatitis C in patients with chronic kidney disease. World J Gastroenterol. 2015;21(2):408-422.
5. American Association for the Study of Liver Diseases, Infectious Diseases Society of America. Recommendations for testing, managing, and treating hepatitis C. http://hcvguidelines.org. Accessed February 15, 2015.