Hepatol Res. 2014 Oct;44(10):E257-60. doi: 10.1111/hepr.12207.

Usefulness of combined application of double-filtration plasmapheresis and twice-daily injections of interferon-β in hemodialysis patients with hepatitis C virus genotype 1b infection and a high viral load.

Zeniya M, Nakano M, Saeki C, Yokoyama K, Ishikawa T, Takaguchi K, Takahashi H.

Gastroenterology, Jikei University Graduate School of Medicine, Tokyo, Japan.

 

Abstract

Hepatitis C virus (HCV) infection is common among hemodialysis (HD) patients and has been recognized as an important prognostic factor. Therefore, the aggressive antiviral therapy is necessary for HCV infection in HD patients. However, various treatment limitations exist in HD patients such as the inability to use ribavirin. We have previously reported that HCV RNA can be eradicated by administration of interferon (IFN)-β during HD in patients with HCV infection caused by genotypes known to be sensitive to IFN therapy and low serum HCV RNA levels. In this case report, we tried to clarify the efficacy of combined application of double-filtration plasmapheresis (DFPP) and IFN-β in HD patients with HCV genotype 1b infection and high serum HCV RNA levels. We report two HD patients with HCV genotype 1b infection and high viral loads who were successfully treated by five sessions of DFPP undertaken prior to treatment with IFN-β (twice-daily injections for 2 weeks). HCV was eradicated by this combination therapy in both patients. We revealed the efficacy of combined application of DFPP and IFN-β in HD patients with HCV genotype 1b infection and high serum HCV RNA levels. This combined therapy may be useful for the HD patients who are resistant to conventional IFN monotherapy.

KEYWORDS: double-filtration plasmapheresis; hemodialysis patients; hepatitis C virus infection; interferon-β

PMID: 23855529

 

Supplements:

The prevalence of hepatitis C virus (HCV) infection in patients receiving chronic hemodialysis (HD) because of renal failure is high, about 10% throughout the world. With favorable management of nephrogenic anemia that leads to less frequent transfusion, increased rate of the use of disposable devices, and guidelines established by academic societies, less people have newly acquired infection these days. However, the incidence of HCV infection is high among middle-aged and older patients receiving HD continuously for a long period, especially that their cancer risk is higher. After the infection is acquired, it shows slow but certain progression and leads to hepatic cirrhosis. The incidence of hepatocellular carcinoma in patients with hepatic cirrhosis is about 6–8% per year. Especially in elderly patients, the incidence is much higher. A report that examined prognostic factors in patients with HCV infection who were receiving HD showed that liver disease-related deaths were the most important factor. While the above actual status is clear, no active intervention for the treatment of HCV infection has been performed. The first reason for this is that the progression of disease condition could not be understood correctly because of HD patients’ low serum transaminase (aspartate aminotransferase [AST], alanine aminotransferase [ALT]) levels, which is key to understanding liver disease conditions caused by HCV infection. The patients were considered to be in a state with persistently normal ALT (PNALT) levels, and their natural histories were not clear at all. The therapeutic results of interferon (IFN) monotherapy for HCV infection were unfavorable, and the concomitant administration of ribavirin to increase the therapeutic effect of IFN was not performed in HD patients in whom hemolysis was unavoidable because of its pharmacokinetics. Interestingly, the clearance rate of HCV infection with IFN monotherapy in the HD patients was significantly higher than that in the patients without HCV infection.

The authors reported that the favorable clearance rate of HCV could be obtained with the administration of IFN-β, which causes fewer adverse reactions than the widely used IFN-α into the HD circuit at the time of HD in patients with low genotype 2 or 1b HCV viral loads who were expected to obtain the effect of IFN monotherapy.

However, its therapeutic effect was unfavorable in many patients with high genotype 1 HCV viral loads. The authors found that viral clearance could be achieved even in patients who could not be treated with IFN monotherapy with virus removal by double membrane hemodiafiltration with the administration of IFN-β, which enhances IFN gene expression, in 2 divided doses. For HCV infection, IFN-free oral therapy with direct-acting antivirus agents (DAAs) has mainly been performed in recent days. However, many DAAs cannot be administered to patients with renal failure. The authors recently experienced more than 90% of HCV clearance by administering a combination therapy with daclatasvir and asunaprevir, which can be administered to patients with renal disorder and genotype 1b HCV infection. However, the combination therapy cannot be performed in patients with genotype 2, and sofosbuvir, a first-line DAA, cannot be administered to patients with renal failure. Thus, the IFN-β therapy for HD patients reported herein, which causes fewer adverse reactions and can be performed for a long period or in 2 divided doses depending on individual patients, should be further examined in the future.

 

 

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