Hepatitis C and lymphoproliferative disorders: from mixed cryoglobulinemia to non-Hodgkin's lymphoma.

BACKGROUND & AIMS: Hepatitis C virus is associated with both mixed cryoglobulinemia and non-Hodgkin's lymphoma, particularly B-cell non-Hodgkin's Lymphoma. Although there are geographic discrepancies in the incidence and prevalence of hepatitis C virus-related lymphomas, large epidemiologic studies and meta-analyses confirm this relationship in both patients with and without mixed cryoglobulinemia. Other factors such as gene translocation, somatic hypermutation and direct infection may also play a role in the malignant transformation of B-cells. METHODS: Recent advances in our understanding between the complex relationship between hepatitis C virus and its interactions with cell proteins on B-cell surface membranes has led to proposed mechanisms on how hepatitis C virus leads to chronic antigenic stimulation resulting in lymphoproliferation. RESULTS: Hepatitis C virus is more weakly associated with T-cell lymphomas, Waldenstrom's macroglobulinemia and other monoclonal gammopathies. Remission of mixed cryoglobulinemia is strongly associated with reduction of hepatitis C virus viral load and recurrence of disease corresponds with viral relapse. Similarly, some studies have shown complete remissions of low grade lymphomas with sustained viral response after antiviral therapy for hepatitis C virus. CONCLUSIONS: Further studies are needed to more clearly understand the pathogenesis and management of hepatitis C virus-related lymphoproliferative disorders.

Recurrence of hepatocellular carcinoma and hepatitis B reinfection in hepatitis B surface antigen-positive patients after liver transplantation.

Hepatitis B virus (HBV) reinfection and recurrence of hepatocellular carcinoma (HCC) after orthotopic liver transplantation (OLT) are associated with increased graft failure and reduced patient survival. We evaluated the effects of both HCC recurrence and HBV reinfection on the long-term survival of these patients after OLT. One hundred seventy-five patients underwent OLT for HBV-related liver diseases and were the subjects of this retrospective study. We assessed risk factors for HBV reinfection, HCC recurrence, and survival post-OLT using univariate and multivariate analyses. During a mean follow-up of 43.0 +/- 42.0 months, 88 of 175 (50.3%) patients transplanted for HBV-related liver disease had HCC prior to OLT. Thirteen (14.8%) of these patients had HCC recurrence after OLT. The mean time for recurrence of HCC was 26.1 +/- 31.9 months. Twelve of 175 (6.9%) patients developed HBV reinfection after liver transplantation. The mean time for HBV reinfection was 28.7 +/- 26.4 months. Ten of these 12 (83.3%) patients had HCC prior to OLT, and 5 (50%) developed recurrence of HCC. On multivariate analyses, pre-OLT HCC and recurrence of HCC post-OLT were significantly associated with HBV reinfection after transplantation (P = 0.031 and P < 0.001, respectively). HCC recurrence after OLT was associated with lymphovascular invasion (P < 0.001) and post-OLT chemotherapy (P < or = 0.001). The 3- and 5-year survival rates were significantly decreased in patients with HBV reinfection (P = 0.007) and in patients with HCC recurrence after OLT (P = 0.03). In conclusion, pre-OLT HCC and HCC recurrence after transplantation were associated with HBV reinfection and with decreased patient survival. Hepatitis B immunoglobulin and antiviral therapy was only partially effective in preventing HBV reinfection in patients with HCC recurrence.