Type III Cryoglobulinemia Associated with Non-Alcoholic Steatohepatitis in the Absence of Chronic Hepatitis C: 820

Purpose: Type III cryoglobulinemia is associated with liver disease from chronic Hepatitis C (HCV). Cryoglobulinemia has never been associated with nonalcoholic steatohepatitis (NASH) without HCV. We present the first case report ever of Type III cryoglobulinemia associated with NASH without HCV infection. Case Presentation: A 44-year-old male presented with six weeks of bilateral lower extremity purpuric rash and arthralgias. His past medical history was notable for hypertension, mildly elevated liver function tests, and recent pneumonia treated with Moxifloxacin. His other medication was Flonase for seasonal allergies. He denied tobacco, alcohol, or illicit drug use. There was no family history of liver or autoimmune disease. Physical exam was only significant for a large purpuric rash on his lower extremities bilaterally. Laboratory evaluation was significant for AST 96 IU/L and ALT 112 IU/L. Serologic testing for HBV, HCV, ceruloplasmin, alpha-1 antitrypsin, anti-LKM1 and hemochromatosis were negative. TMA for HCV was negative. Anti-nuclear antibody and anti-smooth muscle antibody were both low-titer positive at 1:40. Rheumatoid factor was positive at 51 IU/ml. Extractable nuclear antigen panel including RNP-smith, anti-SSA, anti-SSB, SCL-70, and anti-Jo-1 as well as P-ANCA were negative. Anti-cardiolipins were normal. His complement 4 levels were 2 mg/dl (ref: 16-38 mg/dl) and complement 3 was 75 mg/dl (ref: 75-152mg/dl). Immunoglobulins, light chains and SPEP were normal. Cryoglobulins were present in the serum consistent with Type III cryoglobulinemia. Left thigh biopsy revealed superficial acute leukocytoclastic vasculitis. Liver biopsy revealed mixed micro- and macrovesicular steatosis involving 80% of the hepatic parenchyma with mild portal chronic inflammation and balloon cell changes consistent with non-alcoholic steatohepatitis (NASH). Bridging fibrosis was also apparent on liver biopsy. He was treated with prednisone resulting in a rapid improvement in his rash and arthralgias. As the steroids were tapered, he was started on Cellcept 1 gram twice daily. When the patient opted to stop the Cellcept one year later, he developed recurrence of the rash and arthralgias. Reinitiation of immunosuppression resulted in resolution of rash and arthralgias. Discussion: HCV is the most common liver disease associated with cryoglobulinemia. However, cryoglobulinemia has been described in patients without HCV. We report a case of cryoglobulinemia associated with NASH. In cases of cryoglobulinemia in patients who are HCV-negative, we advocate searching for other causes of liver disease. Future studies will need to evaluate a possible relationship between NASH and cryoglobulinemia.