Radiation-induced hepatitis B virus reactivation in hepatocellular carcinoma: A case report

Abstract

Abstract. Hepatitis B virus (HBV) reactivation associated with radiotherapy is rare. The present study reports the case of a 46-year-old man that experienced fatal HBV reactivation. The patient suffered from hepatocellular carcinoma (HCC) with portal vein tumor thrombus, which was treated by radiotherapy at a daily fraction of 2 Gy over 5 weeks, up to a total radiation dose of ~50 Gy. The patient presented with fatigue, yellow sclera and abdominal distension ~8 weeks subsequent to the administration of radiotherapy. The liver function tests, including the level of total bilirubin and prothrombin time, suggested acute-on-chronic liver failure. The serum HBV-DNA level had also increased between undetectable levels and 7.2x10 4 copies/ml. Although the present patient with HCC was treated with 0.5 mg/day entecavir for 8 weeks, in addition to radiotherapy, radiation-induced HBV reactivation occurred. The condition of the patient worsened gradually. The present study emphasizes the importance of liver function and HBV-DNA screening and pre-emptive antiviral prophylaxis prior to radiotherapy in patients with HCC. IntroductionHepatitis B virus (HBV) infection is a serious and common global public health problem (1). It is conservatively estimated that >2 billion individuals have been infected with HBV worldwide and 350 million have suffered from chronic HBV infection. In Asia and the majority of Africa, the disease is particularly prevalent and usually acquired perinatally or in childhood (1). In total, 15-40% of the infected patients will develop cirrhosis, liver failure or hepatocellular carcinoma (HCC), which is currently the fifth most frequent cancer and accounts for between 300,000 and 500,000 mortalities per year (2).Curative surgery is currently available for only 10% of patients. Due to the low tolerance of the liver for irradiation, radiotherapy is limited and is therefore not optimal for the treatment of HCC (3). Therefore, chemotherapy has become a main palliative treatment for certain inoperable patients. However, there is a considerable probability for the reactivation of HBV in HCC patients that receive chemotherapeutic drugs, which may be a fatal complication and may lead to disruption in treatment schedules (4). With the development of novel radiotherapy as 3-dimensional conformal therapy or stereotactic radiation therapy, the role of radiotherapy has become of increasing importance in the treatment of HCC, particularly for HCC patients with portal vein tumor thrombus (PVTT) or a tumor diameter <10 cm (3-5).To the best of our knowledge, previous studies have reported the occurrence of chemotherapy-associated reactivation of HBV in the literature (6,7). However, the occurrence of radiotherapy-associated HBV reactivation is rare. Therefore, the present study reports the case of a patient that experienced fatal HBV reactivation during radiotherapy for HCC with portal vein tumor thrombosis (PVTT) formation. Case reportA 46-year-old male patient with a long history as a HBV carrier presented with fatigue, ye...

Hepatitis B Virus Reactivation in a Patient with Nonalcoholic Steatohepatitis 41 Months after Rituximab-containing Chemotherapy

“…Radiotherapy is also believed to be a risk factor of HBV reactivation. Radiotherapy was reported to induce HBV reactivation in patients with hepatocellular carcinoma of the liver (37,38). A previous study suggested that radiation-induced liver toxicity with HBV reactivation arises from a bystander effect on irradiated endothelial cells releasing cytokines (39).…”

Association of Hepatitis B Virus DNA Level and Follow-up Interval With Hepatocellular Carcinoma Recurrence

“…4 The present study found that several antitumor treatments, including TACE, RFA, MWA, PEI, and brachytherapy, were associated with HBV reactivation, which is associated with recurrence of HCC and OS, consistent with previous reports. [19][20][21][22][23] Combining antiviral treatment with conventional antitumor therapy is significantly associated with a reduced HBV reactivation. 24,25 When treating liver cancer (eg, by TACE), some patients developed hepatitis B flares, and their risk was reduced by the use of antiviral drugs.…”

“…Demographic and the Baseline Clinical Characteristics B Virus DNA Level and Hepatocellular Carcinoma Recurrence nonstandard treatment group, and 2.89 (1.26) cm in the standard treatment group (P < .001).Hepatitis B virus DNA levels of more than 10 5 copies/mL were found in 40.6% of the no treatment group, 20.9% of the nonstandard treatment group, and 10.8% of the standard treatment group and levels of 10 5 copies/mL or less in 59.4% in the no treatment group, 79.1% in the nonstandard treatment group, and 89.2% in the standard treatment group. AFP levels greater than 400 ng/mL (to convert to micrograms per milliliter, multiply by 1) were found in 78.2% of the no treatment group,23.3% of the nonstandard treatment group, and 21.5% of the standard treatment group and of 400 ng/mL or less in 21.8% of the no treatment group, 76.7% of the nonstandard treatment group, and 78.5% of the standard treatment group (P < .001). Child-Pugh stage A was found in 74.4% in the no treatment group, 74.4% of the nonstandard treatment group, and 72.3% of the standard treatment group and B in 25.6% of the no treatment group, 25.6% of the nonstandard treatment group, and 27.7% of the standard treatment group.…”

Strategies for prediction and mitigation of radiation-induced liver toxicity

“…Moreover, of six HBV carriers that developed RILD, four showed evidence of HBV reactivation, with two of them progressing to liver failure [ 84 ]. Other investigators have reported HBV reactivation after liver irradiation with 3D-CRT, with one study suggesting that IL-6 produced from endothelial cell damage was implicated in HBV reactivation through bystander effect [ 40 , 85 ]. A prospective study that enrolled 205 patients with HCC demonstrated that concurrent, more intensive therapies and higher HBV DNA levels (>10 4 copies/ml) were independent predictors of HBV reactivation, ultimately recommending prophylactic antiviral therapy for all patients with high levels of HBV DNA, irrespective of the modality chosen for HCC treatment [ 86 ].…”