BACKGROUND: Chronic hepatitis C virus (HCV) infection is associated with liver dysfunction and hepatocellular carcinoma. In patients with normal kidney function, treatment with pegylated interferon (PEG-IFN) and ribavirin (RBV) frequently leads to eradication of HCV. Treatment in dialysis patients has long been controversial and until recently, the use of RBV was considered to be contra-indicated. We used plasma trough levels of RBV to promote tolerance, safety and efficacy. PEG-IFN alfa-2a (40 kD) was chosen because it is cleared predominantly via hepatic metabolism. METHODS: Seven haemodialysis patients with chronic HCV infection were eligible and started with 135 microg PEG-IFN alfa-2a (40 kD) weekly and 200 mg RBV every other day. Dose adaptations were allowed following study guidelines. Genotypes 1 and 4 (five patients) were treated for 48 weeks and genotypes 2 and 3 (two patients) for 24 weeks. HCV-RNA was determined after 12, 24 and 48 weeks (and at 72 weeks for genotypes 1 and 4). RBV trough plasma levels were monitored regularly by HPLC-technique. RESULTS: All patients completed the treatment. In two patients, the PEG-IFN dose had to be reduced to 90 microg/week because of adverse events. To achieve the target range (1.5-2.5 microg/ml) of the plasma trough level, the mean RBV dose was increased to a dose between 133 and 200 mg each day in five patients. Despite an increase of the weekly erythropoietin (Epo) dose, two to a max of four red cell transfusions were given to four patients. A sustained viral response (SVR) was reached in five patients (3/5 with genotype 1/4 and 2/2 with genotype 2/3). CONCLUSION: In our series of seven patients, we were able to use RBV monitoring drug levels in combination with PEG-IFN alfa-2a (40 kD) and achieve high sustained response rates. However, Epo and transfusion requirements may increase. In two patients adverse events were observed, but manageable with dose reduction of PEG-IFN.
BACKGROUND:Chronic hepatitis C virus (HCV) infection is associated with liver dysfunction and hepatocellular carcinoma. In patients with normal kidney function, treatment with pegylated interferon (PEG-IFN) and ribavirin (RBV) frequently leads to eradication of HCV. Treatment in dialysis patients has long been controversial and until recently, the use of RBV was considered to be contra-indicated. We used plasma trough levels of RBV to promote tolerance, safety and efficacy. PEG-IFN alfa-2a (40 kD) was chosen because it is cleared predominantly via hepatic metabolism. METHODS: Seven haemodialysis patients with chronic HCV infection were eligible and started with 135 microg PEG-IFN alfa-2a (40 kD) weekly and 200 mg RBV every other day. Dose adaptations were allowed following study guidelines. Genotypes 1 and 4 (five patients) were treated for 48 weeks and genotypes 2 and 3 (two patients) for 24 weeks. HCV-RNA was determined after 12, 24 and 48 weeks (and at 72 weeks for genotypes 1 and 4). RBV trough plasma levels were monitored regularly by HPLC-technique. RESULTS: All patients completed the treatment. In two patients, the PEG-IFN dose had to be reduced to 90 microg/week because of adverse events. To achieve the target range (1.5-2.5 microg/ml) of the plasma trough level, the mean RBV dose was increased to a dose between 133 and 200 mg each day in five patients. Despite an increase of the weekly erythropoietin (Epo) dose, two to a max of four red cell transfusions were given to four patients. A sustained viral response (SVR) was reached in five patients (3/5 with genotype 1/4 and 2/2 with genotype 2/3). CONCLUSION: In our series of seven patients, we were able to use RBV monitoring drug levels in combination with PEG-IFN alfa-2a (40 kD) and achieve high sustained response rates. However, Epo and transfusion requirements may increase. In two patients adverse events were observed, but manageable with dose reduction of PEG-IFN.
Authors: Roberto J Carvalho-Filho; Ana Cristina C A Feldner; Antonio Eduardo B Silva; Maria Lucia G Ferraz Journal: World J Gastroenterol Date: 2015-01-14 Impact factor: 5.742
Authors: Craig E Gordon; Katrin Uhlig; Joseph Lau; Christopher H Schmid; Andrew S Levey; John B Wong Journal: Clin J Am Soc Nephrol Date: 2009-07-30 Impact factor: 8.237
Authors: B J Brennan; K Wang; S Blotner; M O Magnusson; J J Wilkins; P Martin; J Solsky; K Nieforth; C Wat; J F Grippo Journal: Antimicrob Agents Chemother Date: 2013-09-30 Impact factor: 5.191