NIV Congres

Case report: A 61-year old female with a history of ankylosing spondylitis, for which she had used prednisolone and recently started TNF-α-inhibitors, was analyzed for an elevation of the erythrocyte sedimentation rate without focal complaints in May 2011. Diagnostic testing demonstrated a lymphoplasmocytic lymphoma (M. Waldenström) with IgM-lambda paraproteinemia. A CT of chest and abdomen did not show lymphoma localization outside the bone marrow. In January 2012 a rise in paraprotein to 36.2 g/L, an increase in spleen diameter and abdominal lymphadenopathy were demonstrated, and chemotherapy with rituximab-cyclophosphamide-vincristine-prednisolone (R-CVP) initiated.

In May 2012 the patient presented with severe hepatitis with a rise in AST/ALT within days to approximately 1000 U/l. Viral serology demonstrated active hepatitis B infection (HBsAg-positive, anti-HBs-negative, HBc-negative, anti-HBc-positive, genotype A, copies 2.8 million/ml). Liver ultrasonography showed no structural abnormalities. The patient probably acquired the virus perinatally, as her mother was hepatitis B-infected. She was referred to the hepatologist for entecavir treatment.

From October 2012 there was evidence of rapidly progressive liver cirrhosis with refractory ascites under dietary salt/fluid restriction and diuretics, requiring frequent drainage despite midodrine therapy. In December 2012 the patient died of upper gastrointestinal hemorrhage.

Discussion: In patients with medical conditions requiring immunosuppressive therapy, specifically chemotherapy and TNF-α-inhibitors, screening for hepatitis B may be required. In chronic infection with HBsAg-positivity reactivation is quite common, ranging from 14-21% after treatment for solid cancers to 24-73% after treatment for lymphoma. In apparently resolved infection (e.g. HBsAg-negative, anti-HBc-positive), reactivation can also been seen. Screening has been advocated for high risk patients (i.e. immigrants from endemic areas, intravenous drug users), but also for all patients receiving intensive chemotherapy. In the Netherlands, however, no universal protocol is implemented.

Chronic carriers of hepatitis B should be treated with prophylactic antiviral therapy such as lamivudine during rituximab treatment and for at least six months after stopping the rituximab. Patients with either positive HBsAg or anti-HBc should be tested for HBV-DNA and treated with prophylaxis in case of HBV-DNA positivity. In case of HBV-DNA negativity, close monitoring of liver enzymes and HBV-DNA up to six months after stopping rituximab is recommended.

Conclusion: We present a case demonstrating hepatitis B reactivation with rapid evolvement to fatal liver cirrhosis after rituximab-containing chemotherapy for M. Waldenström in a patient with probable chronic carriership of hepatitis B. The case underlines the importance of a protocol for hepatitis B screening of patients who will be receiving immunosuppressive therapy.