Interferon‐based therapy for dialysis patients with chronic hepatitis C: Progress and challenges (Editorial)

Chronic hepatitis C virus (HCV) infection is common in dialysis patients, with the reported prevalence varying from 3% to 80% worldwide. Despite the implementation of anti-HCV screening for blood products since early 1990s, the annual incidence of new HCV infection remains substantial (~2.9%) in the dialysis population. Moreover, persistent viraemia after acute HCV infection in dialysis patients ranged from 65.4% to 91.8%. Compared with the general population, the higher prevalence and incidence of HCV infection in patients on maintenance dialysis suggest the route of nosocomial transmission, to which dialyser reuse, internal contamination of haemodialysis machines, contamination of the hands of staff members or shared items between patients may contribute. Dialysis patients with newly acquired HCV infection usually present with mild symptoms and a moderate rise of serum aminotransferase levels, which make early diagnosis of HCV infection difficult. The natural course of chronic HCV infection remains undetermined in this special clinical setting, partly because of the high morbidity and mortality rates of comorbid diseases, which make long-term consequences of HCV infection difficult to establish. A recent international collaborative survey found that an excess of hepatocellular carcinoma (HCC) in dialysis patients was related to the high prevalence of chronic hepatitis B virus or HCV infection. Prospective studies also showed anti-HCV seropositivity and positive HCV RNA were risk factors for mortality. In addition, cirrhosis and HCC accounted for 8.4% and 5.5% of all death in antiHCV-positive patients, respectively. Although dialysis patients may undergo renal transplantation (RT) and patients with chronic hepatitis C undergoing RT usually have a higher survival rate than those on maintenance dialysis, previous studies have shown that these patients have a poor patient and graft survival 7–20 years after RT. In addition, extensive and progressive hepatic fibrosis after RT were also observed, suggesting immunosuppression following RT may worsen the course of hepatic fibrosis and renal graft function in chronic hepatitis C patients. Taken together, these lines of evidence indicate that HCV infection in the dialysis population is an important issue to be tackled. Interferon (IFN)-based treatment for chronic hepatitis C has been the mainstay therapy in immunocompetent patients. In dialysis patients, treatment with standard or pegylated IFN has also received much attention recently. Two meta-analyses evaluating the efficacy and safety of standard IFN monotherapy showed that the sustained virological response (SVR) rates were 37% and 33%, respectively; and the corresponding dropout rates were 17% and 29.6%, respectively. The SVR and dropout rates were higher than those with normal renal function, possibly because of a lower IFN clearance rate. The efficacy and safety of pegylated IFN alpha-2a and -2b in treating dialysis patients showed conflicting results, with a more favourable outcome of patients treated with pegylated IFN alpha-2a (135– 180 mg/week: SVR 50–75%, well tolerated) than those treated with pegylated IFN alpha-2b (0.5–1.0 mg/week: SVR 12.5%, poorly tolerated), which may result from different pharmacokinetic profiles between these two pegylated IFN. Currently, IFN is not generally recommended in RT patients because of the high risks of acute graft rejection, and the low response rate resulting from concomitant use of immunosuppressive agents. However, the long-term virological response can be maintained after RT when successful eradication of HCV by IFN-based therapy was achieved in the dialysis stage. Ribavirin, which has been used in combination with IFN to treat chronic hepatitis C in the general patients and achieve a higher SVR rate than IFN monotherapy, is considered contraindicated in dialysis patients with chronic hepatitis C because of the risk of severe haemolytic anaemia. However, the notion has been challenged recently. Some pilot studies evaluating combined standard IFN alpha plus low-dose ribavirin (170–300 mg/day) showed SVR rates of 17–66% after 24–48 weeks of treatment. In addition, a recent study including six patients with combination of pegylated IFN alpha plus low-dose ribavirin also showed an SVR rate of 50%. Nevertheless, more prospective studies are needed to confirm the safety and the optimal dosage of ribavirin in patients with end-stage renal disease. In brief, treatment of chronic HCV infection with IFN in patients with end-stage renal disease is recommended to be administered at the dialysis stage and with a lower dosage. However, when to start antiviral therapy with which regimen, and what is the long-term treatment outcome remain as a challenging task to practising nephrologists and hepatologists. In this issue of the Journal, Chan et al. conducted a pilot study evaluating the safety and efficacy using pegylated IFN alpha-2a 135 mg/week to treat six dialysis patients with chronic hepatitis C. In this study, all patients tolerated treatment well and SVR was achieved in two (33%) of six NEPHROLOGY 2007; 12, 8–10 doi:10.1111/j.1440-1797.2006. 00703.x