Occult Hepatitis B Flare-up after Chemotherapy Treatment in HBsAg Negative Patient ()
1. Introduction
Hepatitis B virus (HBV) infection is by far the most common chronic viral infection affecting the liver in the world, with over 400 million subjects infected, and it is the leading cause of cirrhosis and hepatocellular carcinoma [1]. Reactivation of HBV in patients undergoing immunosuppressive therapy is a well-recognized complication of considerable clinical importance [2]. The majority of cases of HBV reactivation have been reported to occur shortly after the withdrawal of chemotherapy or during the interval between chemotherapy cycles [3]. HBV screening should be considered for all patients going to receive chemotherapy and other immunosuppressive regimens which have the potential to induce reactivation of HBV infection.
2. Case Report
A 70 year old Caucasian male with past medical history significant for hypothyroidism, hypertension and recently diagnosed Stage 4 Mantle Cell Lymphoma and had received 5 cycles of R-CHOP therapy, with recent PET/CT scans indicating great response to therapy, was admitted to our service with complaints of abdominal pain, nausea and vomiting after 5th cycle of R-CHOP. Prior to therapy, acute hepatitis profile including HBsAg was negative. Baseline serum AST, ALT, INR, albumin, bilirubin and creatinine were within normal limits.
After the 5th cycle of R-CHOP, patient developed abdominal pain, nausea and vomiting to the point that he could not tolerate the last chemotherapy. Gradually, the patient became jaundiced, and complete metabolic profile showed serum AST 423, ALT 307, Total bilirubin 1.9, alkaline phosphatase 82, albumin 3.3, platelets 258 and creatinine 0.95. Repeat Acute hepatitis profile came positive for HBsAg. The patient was admitted to the hospital 10 days later for worsening abdominal pain, jaundice, nausea, vomiting and diarrhea. On physical examination, the patient had normal vital signs, sclera were icteric, there was obvious jaundice, and the liver was mildly enlarged with mild to moderate tenderness to palpation in right upper quadrant. Laboratory data showed reactive HBcAg, HBsAg, HBsAb and positive HBV DNA by PCR. Serum ANA and H282Y gene mutation were negative. There was evidence of worsening of liver function tests with INR 1.77, serum AST 366, ALT 276, albumin 2.6, Creatinine 1.7 and platelets 158. Abdominal and Chest X-rays were normal. Ultrasound of the abdomen showed dilated pancreatic and common bile duct with grade 1 fatty and enlarged liver. MRCP showed no intrahepatic or extrahepatic ductal dilatation. Patient was treated with supportive care and fluid resuscitation. Entecavir was started one week later when liver function failed to normalize. Unfortunately, patient’s condition worsened, and he developed hepatorenal syndrome 2 days after starting Entecavir, which was then discontinued. Lamivudine was recommended but patient did not have a chance to be on this medication. His liver and renal functions worsened gradually with peak total bilirubin 30.8, INR 5.6 and Creatinine 7.23. On the last two days of his life, he also developed disseminated intravascular coagulopathy and was placed on comfort care by family members. Autopsy report was consistent with chronic latent hepatictis B infection.
3. Discussion
Reactivation of HBV causing liver damage is a concern in patients with chronic HBV infections who receive immunosuppressive or cytotoxic treatments. Impairment of the immune response during chemotherapy may lead to resumption of virus replication and infection of more hepatocytes in the absence of an active host immune response. Once the immune response is restored after stopping treatment, a cytotoxic T-cell-mediated response directed against HBV-infected hepatocytes may induce severe liver damage [4,5]. Blanpain et al. showed that chronic HBV infection can be reactivated many years down the road when the host immune system is suppressed [6]. However, the term occult Hepatitis B infection was initially described by Cacciola et al. in 1999 who observed undetectable HBsAg in previously known HBV patients who were concurrently infected with HCV. However, they were able to demonstrate the presence of HBV DNA via PCR technique, hence the term occult hepatitis B infection [7].
Patients who receive chemotherapy are at risk for HBV reactivation after starting the treatment. In one prospective study, Yeo et al. reported reactivation of chronic HBV infection in 20% of the patients undergoing cytotoxic chemotherapy [8]. On the other hand, Lok et al. reported that 67% of patients who were HBsAg-positive developed reactivation during cytotoxic therapy for lymphoma and a small number of patients who were HBsAg-negative experienced the reactivation [9]. Currently, the consensus is to screen the patients for chronic hepatitis B infection with HBsAg prior to starting chemotherapy for cancer treatment [10]. There are no recommendations for further testing on patients who are screened HBsAg-negative. For patients who are HBsAg positive, the use of Lamivudine has been shown in several prospective studies to reduce reactivation of HBV significantly [11,12]. Currently, there are no clear Recommendations on the management of the patients with previously known HBV infection who are seronegative for HBsAg prior the chemotherapy [10], since the incidence of reactivation is substantially lower than those who are HBsAg-positive [8].
4. Conclusions
Reactivation of HBV is a concern in patients with chronic HBV infections who receive immunosuppressive or cytotoxic treatments. HBV screening should be considered for all patients going to receive immunosuppressive regimens which have the potential to induce reactivation of HBV infection. In our case report, we have tried to bring to attention the need for further investigation or screening modality besides using HBsAg as the screening test in patients before starting antineoplastic or immunosuppressive therapy.