Our patient was in apparent good health until the age of 73 when he underwent percutaneous angioplasty for acute non-Q myocardial infarction, after which he was prescribed anticoagulant and antihypertensive therapy. At the age of 77, he had an outpatient medical visit because of the first manifestation of purpura of the lower limbs, arthralgia and a sense of postural instability, raising the suspicion of a cryoglobulinemic syndrome. At this time, the cryocrit was positive (35%), and the patient underwent several serological and molecular investigations that excluded HCV (negative anti-HCV and HCV RNA) and HIV infection and demonstrated chronic HBV infection (surface antigen of the hepatitis B virus (HBsAg) 11 700 IU/mL, anti-HBsAg negative, hepatitis B core antibody positive, anti-hepatitis Be antibody positive, HBV-DNA 2 410 000 IU/mL, anti-HDV negative). Immediately after, he was admitted to our unit because of the onset of a hypertensive crisis that was not controlled by the administration of calcium antagonists, beta-blockers and loop diuretics. Renal function monitoring demonstrated the following values: creatinine 1.85 mg/dL, creatinine clearance 20 mL/min and 24-h proteinuria 1.3 g/24 h. Echotomographic examination showed ultrasonographic signs of cirrhosis, and hepatic elastometry yielded a stiffness value of 47.2 kPa. Other laboratory tests demonstrated aspartate aminotransferase × 6.7 upper limit of normal (ULN), alanine aminotransferase × 4.9 ULN and gamma-glutamyl transpeptidase × 5.2 ULN, and total bilirubin 1.8 mg/dL. On the basis of these data, the patient was started on antiviral treatment (0.5 mg entecavir every 72 h) and prednisone, 50 mg/d, to be tapered to 10 mg/d. Although the hypertensive crisis could presumably be ascribed to a cryoglobulin-induced nephropathy attributable to HBV, considering that the serum β2-microglobulin levels were markedly increased (7.2 mg/L, < 2 ULN) and gamma-globulin showed a monoclonal peak, we also considered the possibility of cryoglobulinemia associated with a myeloproliferative disorder. The characteristics of the cryoprecipitate were therefore evaluated in order to define the type of cryoglobulinemia. We found rheumatoid factor positivity, lower C3 and C4 levels, 24% cryocrit, while serum immunofixation showed a K monoclonal IgM component, and cryocrit immunofixation a K monoclonal IgM component with polyclonal IgG. On the basis of these elements we made a diagnosis of mixed cryoglobulinemia type 2, that did not exclude a myeloproliferative disorder, so a peripheral blood smear and bone marrow biopsy were performed, and these excluded a myeloproliferative disease. During the period of hospitalization we observed an improvement in renal function (creatinine decreased to 1.4 mg/dL, 24-h creatinine clearance increased to 35 mL/min, and 24-h proteinuria decreased to 0.9 g) and a striking reduction of the cryocrit (6.1%). Surprisingly, cryoprecipitate characterization demonstrated the presence of HCV RNA (807 copies/mL, by m2000 Real Time System, Abbott, IL, United States, Figure ) and for this reason, we rechecked the serum anti-HCV antibodies and HCV RNA, and the absence of both was confirmed (HCV RNA undetectable using 50 IU/mL as cut-off).
Real time polymerase chain reaction amplification plot for hepatitis C virus RNA. The presence of viral RNA started to become evident after 19.4 cycles and the amount of RNA was 807 copies/mL.