The effect of anemia on the efficacy and safety of treating chronic hepatitis C infection with direct-acting antivirals in patients with chronic kidney disease.

BACKGROUND/AIM: Chronic hepatitis-C infection is a great health burden in Egypt. The effect of anemia on the efficacy and safety of direct-acting anti-viral (DAA) therapies for those with chronic-kidney disease (CKD) has not been evaluated. PATIENTS/METHODS: This single-center retrospective study included 235 renal patients: i.e., 70-CKD patients not on hemodialysis (42 with anemia, 28 without); 40 hemodialysis patients (16 anemic; 24 non-anemic), and 125 kidney-transplant (KTx) recipients (40 anemic; 85 non-anemic). Anemia was defined by a hemoglobin level < 10.5 g/dL. Hemodialysis patients received ritonavir-boosted paritaprevir/ombitasvir. KTx patients received sofosbuvir/daclatasvir. CKD patients with eGFR > 30 mL/min/1.73 m2 received sofosbuvir/daclatasvir. Those with eGFR < 30 mL/min/1.73 m2 received ritonavir-boosted paritaprevir/ombitasvir; 64 non-anemic patients also received ribavirin therapy. RESULTS: Mean age of CKDs was 49.1 years, 43.2 years for HDs, and 45.2 years for KTx patients. Most were male; body-mass index was ~ 23.8. Anemia did not affect the efficacy of DAAs in hemodialysis, CKD, or KTx patients. Most patients achieved a rapid virologic response (RVR), and a 12- and 24-week sustained viral response. Worsening of anemia among the non-anemic group was mostly related to ribavirin therapy in hemodialysis patients (11/16 patients). Acute kidney injury in CKDs occurred more frequently within the anemic group (59.5%) compared to the non-anemic group (32.1%). For KTx, graft impairment was more common among the anemic group (7/40) compared to the non-anemic group (2/85). CONCLUSION: Hemoglobin levels of < 10.5 g/dL prior to DAA treatment did not affect the virological response in renal patients but was associated with increased serum creatinine among KTx and those with CKD.

High rate of acute kidney injury in patients with chronic kidney disease and hepatitis C virus genotype 4 treated with direct-acting antiviral agents.

BACKGROUND: Direct-acting antivirals (DAAs) have significantly improved the efficacy and safety of treating chronic hepatitis C (CHC), but their effectiveness and safety among patients with chronic kidney disease (CKD) remains poorly understood. Sofosbuvir/daclatasvir regimen is supposed to be used for patients with creatinine clearance more than 30 mL/min, while ombitasvir/paritaprevir/ritonavir regimen is used for patients with creatinine clearance less than 30 mL/min. AIM: The aim of the study was to assess the safety and efficacy of DAAs among patients with CKD. METHODS: Eighteen CKD stage 2-3b patients received sofosbuvir for 3 months. In addition, 42 CKD stage-4 patients received ritonavir-boosted paritaprevir plus ombitasvir for 3 months. Finally, ribavirin was added for 30 of them. RESULTS: The patients'age was 49.2 ± 12 years. Baseline serum creatinine was 3.76 ± 1.67 mg/dL. Fifty patients were HCV genotype 4. A 3-month sustained viral response was achieved in 56 patients and 49 patients achieved a 6-month viral response. There were 11 relapsers. Acute kidney injury (AKI) upon CKD (AKI/CKD) occurred in 28 patients, of which 20 needed hemodialysis. Fifteen/28 recovered from AKI, whereas 13 were maintained on hemodialysis. In multivariate analysis, there were only two independent risk factors for developing AKI/CKD, i.e., being cirrhotic as defined by baseline abdominal ultrasound findings [odds ratio 4.15 (1.33-12.97); p = 0.013] and having had as DAA therapy OMV/PTV/RTV [odds ratio 7.35 (1.84-29.35); p = 0.001]. CONCLUSION: Treatment of HCV among stage 2, 3a, and 3b patients was achieved safely with a sofosbuvir-based regimen. We recommend that stage-4 patients wait until starting hemodialysis or transplantation.

Efficacy and safety of the new antiviral agents for the treatment of hepatitis C virus infection in Egyptian renal transplant recipients.

PURPOSE: Hepatitis C virus (HCV) infection in kidney transplant recipients (KTRs) is common and can impact on patient and graft survival rates. The efficacy and safety of direct-acting antivirals (DAAs) to treat genotype-4 HCV-infected KTRs have not been fully established. METHODS: A prospective, single-arm, single-center study was conducted at Mansoura Urology/Nephrology Center (Mansoura University, Egypt). 114 HCV RNA(+) genotype 4 KTRs were enrolled in this study after a hepatology consultation and consented to start treatment with interferon-free DAAs. A sofosbuvir-based regimen was given to 109 recipients that had creatinine clearance (Crcl) of > 30 mL/min/1.73 m2. Ritonavir-boosted paritaprevir/ombitasvir was prescribed to five recipients with Crcl < 30 mL/min/1.73 m2. RESULTS: The mean age of the cohort was 45.2 ± 11.2 years; most were male. The mean duration with a transplant was 14.2 ± 3.5 years, with different immunosuppressive regimens, mostly based on calcineurin inhibitors. A rapid virological response (RVR), i.e., clearance of viral load, was achieved in 100% at 4 weeks after starting treatment. All patients had a sustained virological response (SVR) at 12 and 24 weeks posttreatment, with one exception. During DAA therapy serum creatinine increased in 12 patients. In three, this was concomitant with elevated calcineurin inhibitor and sirolimus trough levels. Graft biopsies were performed in 8 of these 12 patients: these revealed an acute rejection in 4 cases (acute cellular rejection grade-1A: n = 2, and grade-1B: n = 2). The rejection episodes occurred at 4-6 weeks after starting treatment. CONCLUSION: DAAs were highly efficacious and safely treated genotype-4 HCV-infected KTRs and had no significant adverse effects on graft function/survival.

Treatment of hepatitis C infection among Egyptian hemodialysis patients: the dream becomes a reality.

BACKGROUND AND AIMS: New direct-acting antiviral drugs have become the corner-stone treatment for HCV infection: they show promising results with accepted side-effects and low dropout rates. One of the available regimens is paritaprevir/ombitasvir/ritonavir (PTV/OMV/RTV). Our aim was to study the efficacy and safety of this drug regimen among HCV-positive hemodialysis patients. METHODS: This prospective single-center study was performed in the Urology and Nephrology Center, Mansoura University, Egypt. Ninety-six maintenance hemodialysis patients were screened for HCV antibodies. Positive results were found in 46 patients (47.9%). HCV PCR was assessed in all HCV-antibody-positive patients; positive results were found positive for 38 (82%); all patients were HCV genotype 4. Four patients were excluded due to advanced liver cirrhosis, liver malignancy, or metastatic breast cancer. Thirty-four patients were prescribed PTV/OMV/RTV for 3 months to treat HCV. RESULTS: Mean age was 43.2 ± 11.9 years. Most patients were male (67.6%). There was a rapid response to treatment: HCV PCR became negative by 4 weeks after starting treatment. By 12 and 24 weeks post-DAA therapy, there was a sustained viral response (SVR 12, SVR 24) in 100% of patients with improved liver-enzyme levels. CONCLUSION: The PTV/OMV/RTV regimen was safe and effectively treated Egyptian HCV-positive genotype-4 hemodialysis patients.

Treatment of Chronic Hepatitis C Infection Among Egyptian Kidney Transplant Recipients: A Pilot Study.

OBJECTIVES: Chronic hepatitis C infection incidence and prevalence are high in Egypt and represent a major health burden. Hepatitis C virus infection can affect graft outcomes in kidney transplant recipients. Treatment of hepatitis C virus infection among this special group was difficult during the interferon era; however, with advances in direct-acting antivirals, treatment outcomes have become more promising. MATERIALS AND METHODS: This is a pilot, observational, single-center, one arm study that included 50 kidney transplant recipients seen at the Mansoura (Egypt) Urology and Nephrology Center. Patients were consented to receive a sofosbuvir-based regimen as all had creatinine clearance of greater than 30 mL/min/1.73 m2. RESULTS: All patients achieved rapid virologic responses 4 weeks after starting treatment. Forty-nine of 50 patients achieved 12-week and 24-week sustained viral responses. Six patients had increased serum creatinine levels. Four graft biopsies were performed. Anemia was the most common adverse effect among the patients who were maintained on ribavirin. CONCLUSIONS: Treatment of chronic hepatitis C infection has become easier and safe with the advance of new direct-acting antivirals.

Sofosbuvir and Daclatsvir in Treatment of Hepatitis C Virus-related Membranoproliferative Glomerulonephritis With Cryoglobulinemia in a Patient With Hepatitis C Genotype 4.

Direct antivirals showed dramatic response in hepatitis C virus (HCV) eradication, but their effect on extrahepatic manifestations is still unclear. A 49-year-old woman was referred to us suffering from lower limb edema and frothy urine. Renal biopsy was done and she was diagnosed with HCV-related membranoproliferative glomerulonephritis with cryoglobulinemia. Treatment with interferon plus ribavirin, steroid, and cyclophosphamide was tried but failed. After introduction of a sofosbuvir-based regimen to the treatment, sustained virologic response was achieved and nephrotic syndrome remission was induced successfully. We could conclude that HCV-related membranoproliferative glomerulonephritis with cryoglobulinemia could be treated successfully with immunosuppressive drugs plus sofosbuvir and dacalatasvir.