Treatment of Hepatitis C Virus Infection in Patients with End-stage Renal Disease

Chen-Hua Liu; Jia-Horng Kao

Disclosures

J Gastroenterol Hepatol. 2011;26(2):228-239. 

In This Article

Treatment of ESRD Patients with Chronic HCV Infection

IFN Monotherapy

The SVR and treatment-related withdrawal rates of conventional IFN monotherapy (3–6 MU, three times per week) for 24–48 weeks are generally ≤20% and 5–10% in non-uremic patients with chronic hepatitis C.[94] The treatment of ESRD patients with chronic hepatitis C by conventional IFN monotherapy at a dose of 1–6 MU daily to three times per week for 12–48 weeks resulted in SVR rates of 20–71%. The treatment-related withdrawal rates were 0–53% (Table 4).[105–128] Four meta-analysis studies showed that approximately one-third of ESRD patients with chronic hepatitis C who received conventional IFN monotherapy can achieve an SVR.[129–133] However, the corresponding treatment-related withdrawal rates ranged from 20% to 30%. The higher SVR and treatment-related withdrawal rates for conventional IFN monotherapy in ESRD patients than those in non-uremic patients might be explained by altered IFN pharmacokinetics, specifically decreased renal clearance and higher IFN serum concentrations.[133] A low baseline HCV-RNA level, mild liver histology, and treating patients by IFN at a dose of 3 MU for at least 6 months are predictive of SVR.[110,128,150] Patients who achieve an RVR have a high probability of achieving an SVR; those who fail to clear HCV-RNA at weeks 4–8 of treatment have a low likelihood of achieving an SVR.[109,119,128,150]

Pegylated IFN Monotherapy

The SVR and treatment-related withdrawal rates of pegylated IFN monotherapy (pegylated IFN-α-2a at a dose of 180 μg/week; pegylated IFN-α-2b at a dose of 0.5–1.5 μg/kg/week) for 48 weeks were 18–39% and 3–7% in non-uremic patients with chronic hepatitis C.[151,152] Two pharmacokinetic studies showed that the effective concentration in ESRD patients treated with pegylated IFN-α-2a or IFN-α-2b at a dose of 135–180 μg/week or 1 μg/kg/week was comparable to that in non-uremic patients treated with pegylated IFN-α-2a or IFN-α-2b at a dose of 180 μg/week or 1.5 μg/kg/week.[153,154] The treatment of ESRD patients with chronic hepatitis C by pegylated IFN monotherapy at a dose of 135–180 μg/week or 0.5–1.1 μg/kg/week for 24–48 weeks resulted in SVR rates of 0–79%, and treatment-related withdrawal rates of 0–56% (Table 4).[124,128,134–148] Three meta-analysis studies showed that the SVR and treatment-related withdrawal rates in patients receiving pegylated IFN were 31–37% and 23–28%, which are comparable to conventional IFN.[131,132,149] Although patients treated with either conventional or pegylated IFN have similar efficacy and safety on the basis of meta-analysis studies, one head-to-head, randomized trial showed that the overall efficacy and safety in patients treated with pegylated IFN were superior to those treated with conventional IFN.[128]

Similar to ESRD patients who receive conventional IFN monotherapy, a low baseline HCV-RNA level and RVR are positive predictors for SVR in those receiving pegylated IFN monotherapy.[128]

IFN and Ribavirin Therapy

The use of ribavirin in combination with conventional IFN greatly improves SVR rates to 31–43% in non-uremic patients with chronic hepatitis C.[155,156] Ribavirin is considered contraindicated for the treatment of ESRD patients with chronic hepatitis C because of the risk of life-threatening hemolytic anemia. However, several studies showed that using low-dose ribavirin (200 mg three times per week to 400 mg daily) to keep target concentrations of 10–15 μmol/L in combination with conventional IFN and high-dose erythropoietin (20 000–30 000 IU/week) was feasible for treating ESRD patients with chronic hepatitis C. SVR and treatment-related withdrawal rates after 24–48 weeks of combination therapy ranged between 17% and 63%, and 0% and 33%, respectively (Table 5).[157–159] Although these pilot studies showed it might be safe to administrate low-dose ribavirin under close hemoglobin surveillance and high-dose erythropoietin supply, ribavirin is generally not recommended for routine clinical use, unless further large-scale trials confirm its safety profile in ESRD patients.

Pegylated IFN and Ribavirin Therapy

Combination therapy with pegylated IFN and ribavirin has improved the SVR rate and is the current standard of care to treat non-uremic patients with chronic hepatitis C.[166,167] However, only a few studies have assessed the efficacy and safety of pegylated IFN plus low-dose ribavirin to treat ESRD patients with chronic hepatitis C (Table 5).[160–164] SVR and treatment-related withdrawal rates after 24 or 48 weeks of combination therapy ranged between 7% and 97%, and 0% and 71%, respectively. These patients needed to receive high-dose erythropoietin (10 000–40 000 IU/week) to maintain adequate dosage for ribavirin during the treatment to achieve excellent on-treatment viral suppression.[160,161] Furthermore, patients with HCV genotype 2 or 3 infection have higher SVR rates than those with genotype 1 or 4 infection.

Retreatment for Prior Relapsers to IFN Monotherapy

Although the safety and efficacy of conventional or pegylated IFN plus ribavirin to retreat non-uremic patients with chronic hepatitis C who failed to respond to prior IFN-based monotherapy are well established, only two studies have addressed this issue in ESRD patients. Djordjevićet al. retreated four patients who relapsed from 12 weeks of conventional IFN monotherapy at a dose of 3 MU three times per week by the same protocol for another 24 weeks. Despite all the patients having good viral suppression, ALT normalization, and tolerance during the retreatment, none had an SVR.[113]

In 2009, we retreated 35 patients who relapsed from 24 weeks of conventional or pegylated IFN monotherapy with 135 μg/week pegylated IFN and daily 200 mg ribavirin for 48 (HCV genotype 1) or 24 (HCV genotype 2) weeks.[165] The overall SVR rate was 60%, and the SVR rate in the HCV genotype 2 patients was superior to that in the HCV genotype 1 patients (80% vs 52%). The treatment-related withdrawal rate was 17%. Twenty-six (74%) patients had to receive erythropoietin at a mean dose of 15 000 IU/week to manage anemia during combination therapy. Low baseline HCV-RNA and RVR were independent predictors for SVR.

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