Pegylated interferon alpha-2a for treatment of chronic HCV infection in hemodialysis patients: a single Saudi center experience.
BACKGROUND
Chronic hepatitis C infection is common among patients on dialysis. While the associated liver disease is usually relatively mild during dialysis, disease progression can accelerate due to immunosuppression following kidney transplantation, and interferon therapy after transplantation stimulates graft rejection. Pegylated interferon and ribavirin are now the recommended treatment for chronic hepatitis C virus in patients without renal failure. However, until now, there has been relatively little information on the efficacy and tolerability of pegylated interferon in dialysis patients.


OBJECTIVE
To evaluate the response to pegylated interferon alpha-2a in chronic hepatitis C-infected patients on chronic hemodialysis.


METHODS
This controlled study included 28 patients with end-stage renal disease who had been on dialysis in the Prince Salman Center for Kidney Disease for more than 6 months and tested positive for HCV RNA on repeated occasions. Thirteen patients were treated with pegylated interferon alpha-2a therapy (of which three were also receiving ribavirin), and the remaining fifteen served as controls. Viral genotyping and both qualitative and quantitative PCR were carried out before starting therapy. Treatment was continued for 48 weeks. After 24 weeks of treatment, the biochemical and virological responses were evaluated. Biochemical response was evaluated at the end of the treatment, with sustained virological response (SVR) being evaluated 24 weeks later. The side effects were monitored throughout the treatment period.


RESULTS
All patients in the treatment group completed 48 weeks of therapy without any drop out. Their mean age was 43.38 ± 11.62 years. After 24 weeks of therapy, 10 patients (76%) were initial responders, while 3 patients (24%) were resistant. Six months after termination of therapy, 9 patients (69%) were sustained responders, while one patient relapsed. Their ALT and AST dropped from 55.78 ± 33.79 IU/dl and 34.04 ± 19.58 IU/dl before starting therapy to 27.22 ± 16.54 IU/dl and 18.88 ± 12.28 IU/dl after termination (P = .06 and .08, respectively). Their mean hemoglobin (Hb) level dropped from 11.05 ± 1.43 to 9.48 ± 1.24 g/dl (P = 0.3), and white blood cell count (WBC) dropped from 6.82 ± 2.6 × 10(3)/mm(3) to 4.1 ± 2.34 × 10(3)/mm(3); (P = 0.57). Platelet count fell from 194.56 ± 129.78 × 10(3)/mm(3) to (152.33 ± 107.66 × 10(3)/mm(3); P = 0.39). When initial responders (n = 10) were compared to resistant patients (n = 3), the only observable difference was higher ALT and AST levels in resistant patients. Pegylated interferon alpha-2a was well tolerated, and none of the patients stopped interferon because of hematological side effects while dose modification was carried out in most of the patients. All three patients who received combination therapy from the start were sustained responders. None of the patients in the control group seroconverted to HCV negative status during the study period.


CONCLUSIONS
Pegylated interferon alpha-2a was well tolerated among our hemodialysis patients. Hematological disturbances appeared to be the most important adverse effects. At the end of therapy a response rate of up to 76%, with 69% sustained response, can be obtained with pegylated interferon alpha-2a therapy.
Alsaran
Khalid
K
Prince Salman Center for Kidney Disease, Riyadh, Kingdom of Saudi Arabia. khalid_aln@yahoo.co.uk
Sabry
Alaa
A
Shaheen
Naila
N
D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000740:Anemia / Q000209:etiology; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006454:Hemoglobins / Q000378:metabolism; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D006435:Renal Dialysis; D012254:Ribavirin / Q000627:therapeutic use; D012529:Saudi Arabia
D000998:Antiviral Agents; D006454:Hemoglobins; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C100416:peginterferon alfa-2a