| Abstract|| |
To evaluate the response to alpha-interferon (INF) in patients who develop acute hepatitis C virus (HCV) infection during hemodialysis, we studied 17 patients who had infection while on dialysis. We administered three million units of alpha interferon subcutaneously to nine adult patients three times per week for 12 weeks; the rest of the patients served as controls. The patients in both groups were followed for 24 months after the diagnosis of seroconversion to anti-HCV antibody. Serum alanine aminotransferase (ALT) levels, anti-HCV antibody levels and HCV- poly chain reaction (HCV-PCR) were performed at regular intervals during the follow-up. Two patients in the treatment group dropped out; one because of colitis and another because of non-compliance. Of the seven patients who completed the course of therapy, all the patients had normal serum ALT levels in 2-8 weeks of therapy, three (42%) patients converted back to anti-HCV antibodies negative and six (86%) had HCV-PCR negative at 12 weeks of therapy (primary virological response) and remained so till the end of follow-up (sustained virological response). The liver biopsy performed in all the responders to therapy at 4-24 months after completion of treatment showed mild hepatitis. In the control group, all the patients continued to have raised serum ALT levels throughout the study; 12% converted anti-HCV antibodies to negative and HCV-PCR (performed on five patients) remained positive during the whole study period. In conclusion our study suggests the efficacy and safety of alpha interferon in the therapy of acute HCV infection in hemodialysis patients.
Keywords: Hepatitis C, Virus, Hemodialysis, Alpha interferon, Chronic, infection
|How to cite this article:|
Al-Harbi AS, Malik GH, Subaity Y, Mansy H, Abutaleb N. Treatment of Acute Hepatitis C Virus Infection with Alpha Interferon in Patients on Hemodialysis. Saudi J Kidney Dis Transpl 2005;16:293-7
|How to cite this URL:|
Al-Harbi AS, Malik GH, Subaity Y, Mansy H, Abutaleb N. Treatment of Acute Hepatitis C Virus Infection with Alpha Interferon in Patients on Hemodialysis. Saudi J Kidney Dis Transpl [serial online] 2005 [cited 2020 Dec 5];16:293-7. Available from: https://www.sjkdt.org/text.asp?2005/16/3/293/32857
| Introduction|| |
Almost four million people in the United States of America and 170 million worldwide are estimated to be infected by hepatitis C virus (HCV). , The known sources of transmission are blood transfusion, , needle-stick injury,  sexual exposure,  and intravenous drug abuse.  Following exposure, 20-33% of patients develop symptomatic acute HCV infection.  About 60% of these patients develop chronic hepatitis with a significant proportion progressing to cirrhosis and hepatocellular carcinoma. 
Patients on maintenance hemodialysis have many folds higher prevalence of HCV infection than that in the general population. There is a large variation of prevalence in different parts of the world and sometimes within the same country.  In Saudi Arabia, the mean prevalence of HCV infection in dialysis patients is 68%, which is much higher than the 3.5-5.5% in the general population. 10,11 The mean long-term response rate to therapy of chronic HCV infection is around 40%. 
Treatment of HCV infection in the acute phase by interferon may accomplish high response rate in the general population. A recent meta-analysis study about the treatment of symptomatic acute HCV infection with interferon (both alpha and beta) showed a 90% long-term response rate.  In another study, Jaeckel et al noted 98% response rate to treatment of acute HCV infection with interferon alfa-2b after 24 weeks of follow-up. 
Chronic HCV infection in renal transplant recipients has a detrimental effect on patient and graft survival. , Eradication of HCV is desirable in patients with end-stage renal failure especially candidates for kidney transplantation. , Reports on treatment of acute HCV infection in dialysis patients are scanty. In one report on interferon therapy in hemodialysis patients with acute HCV infection, 65.4% sustained virological response was noted. 
In our study, we evaluate the response to alpha-interferon (INF) in patients who developed acute HCV infection during hemodialysis.
| Materials and Methods|| |
Seventeen patients who developed acute HCV infection while on hemodialysis were included in the study. They were divided into two groups: Group A (treatment group) that included patients who were treated with INF, and Group B (control) that included patients who served as controls.
Patients who had acute hepatitis due to other causes were excluded from the study. All patients included in the study had normal serum alanine aminotransferase (ALT) levels and were anti-HCV antibody negative for at least six months before sero-conversion. All the patients had sero-converted after hemodialysis in other centers while on vacation. The diagnosis of acute HCV infection was based on a rise of twice the normal or more of serum ALT level compared to baseline in addition to a positive serum anti-HCV antibody. The diagnosis of positive anti-HCV antibody was made by third generation enzyme linked immunosorbent assay (ELISA-3) and confirmed by third generation recombinant immunoblot assay (RIBA-3) in all cases.
All the patients in the group A were given INF in a dose of 3 million units subcutaneously 3 times per week for 12 weeks. They continued on their usual dialysis schedule and medications. Serum ALT levels were evaluated twice a week for 2 weeks followed by weekly for 2 weeks and later every 2 weeks till the completion of 12 weeks of therapy followed by routine monthly tests for 24 months. AntiHCV antibody levels were performed at the beginning of the study, after completing therapy (3 months) and at the end of followup (24 months). HCV-PCR was performed after completing 3 months of therapy and at the end of follow up. Liver biopsy was obtained in patients who underwent renal transplantation.
| Results|| |
Group A included nine patients-five males and four females with a mean age of 39 ± 3 (range: 15-58) years. Group B included eight patients - two males and six females with a mean age of 39± 3.5(range: 15-68) years. The patients in both groups were followed for 24 months after the diagnosis of seroconversion to anti-HCV antibody was made.
In group A, two patients dropped out; one because of toxic colitis attributed to INF therapy despite normalized serum ALT levels after 4 weeks of therapy, and the other was noncompliant to follow-up. The other seven patients completed the study; all normalized serum ALT levels in 4.8 ± 0.5 weeks, three (42%) became anti-HCV antibody negative over a period of 12 weeks and remained negative till 24 months of follow-up, and six (86%) turned HCV-PCR negative at 12 weeks (primary virological response) and remained so till the end of follow-up (sustained virological response). All the responders to therapy underwent liver biopsy 4-24 months after completing the course of therapy had mild hepatitis and all of them later underwent renal transplantation.
All the patients in group A developed flu like illness lasting for 24-48 hours following each injection of INF. Two patients whose underlying cause of renal failure was systemic lupus erythematosus developed neutropenia, which improved in both by reducing the INF dose by 50% (1.5 million units each dose). One patient developed thyroiditis characterized by pain in the neck, fever, raised levels of thyroid stimulating hormone and antithyroid antibodies during the third week of INF therapy and it subsided with analgesics without the need to discontinue INF therapy.
In group B, all the patients continued to have raised levels of serum ALT in fluctuating levels till the end of the study, only one (12%) patient converted anti-HCV antibodies back to negative and HCV-PCR performed on five patients was positive and remained so during the follow-up period. None of the patients in this group underwent renal transplantation.
| Discussion|| |
The risk of chronic infection after an episode of acute HCV infection is high; 80-100% of patients remain HCV-PCR positive and 6080% has persistently elevated serum transaminases. , The majority of patients with acute HCV infection are asymptomatic and jaundice is present in fewer than 25%.  Thus, identification of acute hepatitis due to HCV is uncommon and so the opportunity for treatment. The goal of treating patients with acute HCV infection is to reduce the chances of progressing to chronic infection. In dialysis patients, periodic measurement of serum aminotransferases' level and anti-HCV antibodies increases the chances of early diagnosis of HCV infection.
Camma et al, in a meta-analysis of nine studies, concluded that short course of low dose interferon administered to patients with acute HCV infection is significantly more effective than no treatment in obtaining viral clearance and normal aminotransferases 12 months after stopping treatment.  Similar conclusions have been made in other studies. 23],
In a study of interferon therapy in hemodialysis patients with acute HCV infection comparing the outcome in 16 patients treated with low dose (3 million units) and 20 with high dose (6-10 million units) three times per week, there was no statistically significant difference in the sustained virological response between the two groups compared to 17 controls who received no treatment.  We elected in our study to use the lower dose regimen to avoid side effects without compromising efficacy. In the treatment group of our study, the sustained virological response was 85%, which is higher than the 65% reported elsewhere. 
Anti-HCV antibodies may persist after successful antiviral therapy.  In our study, anti-HCV antibodies remained positive in seven out of eight (88%) patients in the control group, whereas anti-HCV antibodies remained positive in only four out of seven (57.1%) of the patients who received interferon..
There is a poor correlation between the biochemical liver function tests and the histological changes in dialysis patients with HCV infection. , The patients in the treatment group of our study underwent liver biopsy as part of pre-transplant assessment 4-24 months after completion of INF therapy. They showed mild hepatitis indicating mild injury from acute HCV infection that was halted by early intervention. The findings of the liver biopsies in our study reflect a good correlation between liver histopathology and biochemical liver function tests in acute HCV infection in response to therapy. However, the number of cases in the present study is small and further studies are needed for confirmation.
Up to 60% of HCV positive patients develop chronic liver disease and worsening of liver disease in the post-transplant period. , Eradication of HCV infection in the acute stage may enable these patients to undergo renal transplantation safely. Pre-transplant INF therapy has no detrimental effect on subsequent renal allograft survival.  In our study, all the patients who completed the course of therapy for acute HCV infection received renal transplantation.
Toxic effects of INF therapy like fever, malaise and arthralgias observed in most of the patients are transient and reversible.  All the patients in our study developed transient "flu" like illness while on INF therapy. Furthermore, transient thyroiditis as a complication of to INF therapy has been described.  One patient in our study developed thyroiditis presenting as neck pain associated with raised thyroid stimulating hormone and anti-thyroid antibodies in the third week of INF therapy, which subsided without discontinuing INF therapy. Another patient who had lupus nephritis developed neutropenia that responded to the reduction of the dose of INF.
In conclusion, our study suggests interferon alpha is both safe and efficacious in the therapy of acute HCV infection in hemodialysis patients.
A short course of 12 weeks of INF therapy has high sustained virological response that will enable such patients to undergo renal transplantation.
| Acknowledgments|| |
The authors feel grateful to Ms. Sesita J. Benedicto for her secretarial assistance in preparing the manuscript.
| References|| |
|1.||Alter MJ, Kruszon-Moran D, Nainan, et al. The prevalence of hepatitis C virus infection in the United States, 1988 through 1994. N Engl J Med 1999;341:556-62. |
|2.||Alter HJ, Seeff LB. Recovery, persistence and sequelae in hepatitis C virus infection: a perspective on long-term outcome. Semin Liver Dis 2000;20:17-35. [PUBMED] |
|3.||Healey CJ, Sabharwal NK, Daub J, et al. Outbreak of acute hepatitis C following the use of anti-hepatitis C virus screened intravenous immunoglobulin therapy. Gastroenterology 1996;110:1120-26. |
|4.||Brink NS, Chopra R, Perrons CJ, et al. Acute hepatitis C infection in patients undergoing therapy for haematological malignancies: a clinical and virological study. Br J Haematol 1993;83:498-503. [PUBMED] |
|5.||Arai Y, Noda K, Enomoto N, et al. A prospective study of hepatitis C virus infection after needlestick accidents. Liver 1996;16:331-4. [PUBMED] |
|6.||Healey CJ, Smith DB, Walker JL, et al. Acute hepatitis C infection after sexual exposure. Gut 1995;36:148-50. [PUBMED] [FULLTEXT]|
|7.||Quin JW. Interferon therapy for acute hepatitis C Viral infection - a review by meta-analysis. Aust N Z J Med 1997;27:611-8. [PUBMED] |
|8.||Alter MJ, Margolis HS, Krawczynski K, et al. The natural history of community acquired hepatitis C in the United States. N Engl J Med 1992;327:1899-905. [PUBMED] |
|9.||Pereira BJ, Levey AS. Hepatitis C virus infection in dialysis and renal transplantation. Kidney Int 1997;51:981-99. [PUBMED] |
|10.||Al-Faleh FZ, Ramia S. Hepatitis C Virus in Saudi Arabia: a review. Ann Saudi Med 1997;17:77-82. [PUBMED] |
|11.||Huraib SO. Hepatitis C in dialysis patients. Saudi J Kidney Dis and Transplant 1995; 6:197-205. |
|12.||Hoofnagle JH, Bisceglie AM. The treatment of chronic viral hepatitis. N Engl J Med 1997;336:347-56. [PUBMED] [FULLTEXT]|
|13.||Jaeckel E, Cornberg M, Wedemeyer H, et al. Treatment of acute hepatitis C with interferon alfa-2b. N Engl J Med 2001;345(20):1452-7. |
|14.||Periera BJ, Wright TL, Schmid CH, Levey A. The impact of pretransplantation hepatitis C infection on the outcome of renal transplantation. Transplantation 1995;60:799-805. |
|15.||Legendre C, Garrigue V, Le Bihan C, et al. Harmful long-term impact of hepatitis C virus infection in kidney transplant recipients. Transplantation 1998;65:667-70. [PUBMED] [FULLTEXT]|
|16.||Gursoy M, Koksal R, Karavelioglu D, et al. Pretransplantation alpha-interferon therapy and the effect of hepatitis C virus infection on kidney allograft recipients. Transplant Proc 2000;32:580-2. |
|17.||Duarte R, Huraib S, Said R, et al. Interferon-alpha facilitates renal transplantation in hemodialysis patients with chronic viral hepatitis. Am J Kidney Dis 1995;25:40-5. [PUBMED] |
|18.||Gursoy M, Gur G, Arslan H, Ozdemir N, Boyacioglu S. Interferon therapy in hemodialysis patients with acute hepatitis C virus infection and factors that predict response to treatment. J Viral Hepat 2001;8:70-7. |
|19.||Farci P, Alter HJ, Wong D, et al. A longterm study of hepatitis C virus replication in non-A, non-B hepatitis. N Engl J Med 1991;325:98-104. [PUBMED] |
|20.||Barrera JM, Bruguera M, Ercilla MG, et al. Persistent hepatitis C Viremia after acute self-limiting post transfusion hepatitis C. Hepatology 1995;21:639-44. [PUBMED] |
|21.||Hoofnagle JH, Carithers RL Jr, Shapiro C, Ascher N. Fulminant hepatic failure: Summary of a workshop. Hepatology 1995;21:240-52. |
|22.||Camma C, Almasio P, Craxi A. Interferon as treatment for acute hepatitis C. A metaanalysis. Dig Dis Sci 1996;41:1248-55. |
|23.||Takano S, Satomura Y, Omata M. Effects of Interferon Beta on Non-A, Non-B Acute Hepatitis: a prospective, randomized, controlleddose study. Gastroenterology 1994;107:805-11. [PUBMED] |
|24.||Karino Y, Toyota J, Sugawara M, et al. Early loss of serum hepatitis C virus RNA can predict a sustained response to interferon therapy in patients with chronic hepatitis C. Am J Gastroenterol 1997;92:61-5. [PUBMED] |
|25.||Gane E, Pilmore H. Management of chronic viral hepatitis before and after renal transplantation. Transplantation 2002;74:427-37. [PUBMED] [FULLTEXT]|
|26.||Pol S, Romeo R, Zins B, et al. Hepatitis C virus RNA in anti-HCV positive hemodialyzed patients: significance and therapeutic implication. Kidney Int 1993;44(5):1097-100. |
|27.||Al-Wakeel J, Malik GH, Al-Mohaya S, et al. Liver disease in dialysis patients with antibodies to hepatitis C virus. Nephrol Dial Transplant 1996;11: 2265-8. [PUBMED] [FULLTEXT]|
|28.||Morales JM, Monoz MA, Castellano G, et al. Impact of hepatitis C in long-functioning renal transplants: a clinicopathological followup. Transplant Proc 1993;25:1450-3. |
|29.||Gursoy M, Bilezikci B, Colak T, et al. Histologic outcome of hepatitis C virus infection in renal transplant recipients and the effect of pretransplantation interferon treatment. Transplant Proc 2000;32:558-60. |
|30.||Borden EC, Parkinson D. Interferons: effectiveness, toxicities and costs. Ann Intern Med 1996;125:614-6. [PUBMED] [FULLTEXT]|
|31.||Roti E, Minelli R, Guiberti T, et al. Multiple changes in thyroid function in patients with chronic active HCV hepatitis treated with recombinant interferon alpha. Am J Med 1996;101:482-6. |
Ali S.B Al-Harbi
Department of Internal Medicine, Security Forces Hospital Program, P.O. Box 3643, Riyadh 11481