SP567STUDY OF HEPATITIS C VIRUS-RELATED CRYOGLOBULINEMIC VASCULITIS IN CHRONIC HEMODIALYSIS PATIENTS

Abstract

Introduction and Aims: Cryoglobulins are immunoglobulins characterized by their insolubility at low temperatures (0-4I) and their dissolution after rewarming. Cryoglobulins are classified as either single (type 1), consisting of a monoclonal immunoglobulin, or mixed, comprising two or more immunoglobulin isotypes, with (typeII) or without (typeIII) a monoclonal component. More than 90% of patients with mixed cryoglobulinemia were infected with hepatitis C virus (HCV). Cryoglobulin can be detected in 25 to 30% of HCV-positive patients. Cryoglobulin-related illness, known as cryoglobulinemic vasculitis, appears in 10 to 15% of the patients. It is also known that HCV infection is rampant among chronic hemodialysis (HD) patients. The effectiveness of interferon in the treatment of patients with mixed cryoglobulinemia was reported. Peripheral artery disease (PAD) is commonly seen in chronic HD patients. Chronic HD patients experience high incidence of limb amputations due to leg ulcers and digital gangrene. The aim of this study is to investigate the clinical characteristics of HCV-related cryoglobulinemic vasculitis and limb amputations in chronic HD patients. Methods: Protocol (1): Data from 2,214 HD patients in Japan from dialysis clinics from 2009 to 2013 were analyzed. Each medical record was assessed for prior amputation(s) of the lower or upper limb, including fingers and toes, on or before entry into the study. Protocol (2): We investigated serum HCV antibody and HBV antigen in 103 HD patients (male/female: 62/41, Age: 60.5±14.7 years). HCV antibody were positive in 8 HD patients (7.8%), HBV antigen were positive in 2 HD patients (1.9%). We determined serum cryoglobulin in 8 HD patients (male/ female: 6/2, Age: 67.3±12.6 years) with HCV or HBV (male 2, Age: 61.5±1.5 years). Results: (1) Seventy-three patients of 2,214 HD patients had a history of amputation. The limb amputation rate was 3.3%. Fifty-three HD patients (72.6%) were male. Fifty-seven HD patients (78.1%) had diabetic nephropathy as the primary cause of end-stage renal disease (ESRD). The mean serum albumin of HD patients with amputation was 3.5±0.4g/dl, high sensitive CRP level was 0.5±1.2mg/dl. HD patients with amputation had a significantly-higher incidence of myocardial infarction than those without amputation (10.9% vs. 1.5%, P<0.05). After 5-year follow up, the mortality of patients with amputation was significantly higher than those without amputation (35.6% vs. 20.5%, P<0.05).(2) Cryoglobulinemia was present in 12.5% of HD patients with HCV infection, 0% of HBV infection. Cryoglobulinemia plus positive HCV (HCV RNA 6.8 Log IU/mL, genotype 2) was accompanied with hypocomplementemia (CH50: 5 U/mL; standard value: 30-45 U/mL) in one HD patient. He started HD three times a week due to diabetic nephropathy in February 2006. He had digital gangrene of his right fourth finger and Raynaund's phenomenon in February 2014. After liver biopy, he was treated with peginterferon alfa-2a (135μg once a week) for chronic HCV infection. After peginterferon alfa-2a therapy for 24 weeks, HCV antibody changed to negative. Thereafter peginterferon alfa-2a therapy was performed, serum cryoglobulin changed to negative and his digital gangrene improved. Conclusions: Those results suggest that general care management including observation of cardiovascular disease was important for HD patients with amputation. The peginterferon alfa-2a therapy was shown to be effective in chronic HD patient with HCV-related cryoglobulinemic vasculitis.