What is the treatment for MPGN in hepatitis C?
The development of cryoglobulinemia is contingent on viral interaction with B cells and subsequent B-cell IgM production to form cryoglobulins.
Therefore reducing the viral load is the most critical step in controlling this disease process. Initially, the only effective therapy for hepatitis C was the use of interferon with or without adjunctive ribavirin. Interferon was poorly tolerated and rarely led to a sustained viral response.
The development of DAAs has revolutionized the therapy of HCV. These drugs inhibit the assembly of non-structural viral capsid proteins and after a 12-week course of therapy often result in a sustained viral remission of >95% regardless of HCV genotype.
In certain circumstances, additional, more aggressive immunosuppressive therapy may be warranted in HCV-related MPGN.
These exceptions include the following:
(1) a rapid decline of kidney function with biopsy evidence of crescentic changes; or
(2) systemic vasculitis with life-threatening organ dysfunction. In these cases, simply controlling the virus will not modify the damage occurring from the cryoglobulins that are already formed and circulating.
The strategy will need to target removing the systemic cryoglobulins so ongoing tissue injury can be attenuated, and then the DAAs can inhibit the new production of IgMk type II cryoglobulins.
Plasmapheresis has become the treatment of choice for severe cases of cryoglobulinemia and will effectively remove these immune complexes from the circulation. Concomitantly, treatment should target the B cells that are producing the abnormal IgMk antibodies.
In past years, chemotherapy, such as the use of cyclophosphamide, was used to inhibit B-cell proliferation. This therapy was not specific to B cells and resulted in potentially serious collateral effects on other cell lines. The use of the monoclonal anti-CD20 antibody, rituximab, selectively removes B cells from the circulation and has revolutionized the therapy of B-cell lymphomas and cryoglobulinemia. Rituximab binds to a surface antigen only found on B cells (CD20) and leads to their peripheral destruction and elimination.
This assists in stopping cryoglobulin production while plasmapheresis removes the antibodies already present.
