Japanese Journal of Clinical Oncology 32:543-545 (2002)
© 2002 Foundation for Promotion of Cancer Research
Reactivation of Hepatitis B Virus Infection in Pancreatic Cancer: a Case Report
lu1
uayib Yalcin1,+1 Hacettepe University Institute of Oncology and 2 Department of Internal Medicine, Hacettepe University, Ankara, Turkey
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
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Impairment of liver function can be seen in cancer patients for a variety of reasons including metastasis, biliary obstruction, toxicity of chemotherapy or other concomittant drugs, can be paraneoplastic or can be due to infections, especially with hepatotropic viruses. Mostly reported in hematological malignancies, reactivation of hepatitis B virus (HBV) is a complication of chronic HBV infection in patients under cytotoxic or immunosuppressive therapy. Up to now, only a few cases of hepatitis B reactivation have been described in patients with solid tumors. We report an acute reversible deterioration of liver function tests following cytotoxic chemotherapy in an HBsAg-positive patient with metastatic pancreatic cancer due to hepatitis B reactivation. As far as we know, this is the first case of pancreatic carcinoma with reactivation following chemotherapy. As experience with acute flares of HBV carriers in solid tumors increases, the establishment of guidelines for the management of these patients has become more crucial.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
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Abnormalities in the liver functions can be seen in cancer patients for a variety of reasons, including metastasis, biliary obstruction, toxicity of chemotherapy or other concomittant drugs, can be paraneoplastic or can be due to infections, especially with hepatotropic viruses (1,2). Mostly reported in hematological malignancies, reactivation of hepatitis B virus (HBV) is a complication of chronic HBV infection in patients under cytotoxic or immunosuppressive therapy (3,4). Some hepatitis B reactivation cases have also been described in patients with solid tumors such as breast and lung cancer and choriocarcinoma (5). We report an acute reversible deterioration of liver function tests following cytotoxic chemotherapy in an HBsAg-positive patient with metastatic pancreas cancer due to hepatitis B reactivation.
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CASE REPORT |
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TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
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A 58-year-old male was admitted to hospital with complaints of abdominal pain and weight loss. Abdominal computed tomography revealed a mass located in the uncinate process of the pancreas and metastatic nodular lesions in the liver. CA19-9 was 2844 U/ml (normal range: 0–34 U/ml). Fine needle aspiration of the pancreas revealed adenocarcinoma, HBsAg (+), antiHBs (–), antiHCV (–). Liver function tests were within normal limits and as follows: AST, 31 U/l; ALT, 20 U/l; ALP, 209 U/l; GGT, 35 U/l; bilirubin, 0.59 mg/dl.
On laparotomy, palliative gastrojejunostomy was performed and biopsies from the liver nodules and peritoneal implants were also reported as adenocarcinoma. Chemotherapy including cisplatin (30 mg/m2) and gemcitabine (600 mg/m2) every 14 days was begun and after five courses of chemotherapy, liver function tests rapidly deteriorated: ALT, 553 U/l; AST, 313 U/l; GGT, 227 U/l; ALP, 604 U/l; total bilirubin (TB), 2.13 mg/dl; HBsAg (+); antiHBs (–); HBeAg (–); antiHbe (+); antiHBcTotal (+); antiHCV (–); antiHDV (–); antiHAV IgM and IgG (–); CEA,2.48 ng/ml (0–5); CA19-9, 1198 U/ml (0–34). HBV DNA measured by the PCR method was 232 pg/ml (normal range: 0–5 pg/ml). Abdominal CT revealed the primary and metastatic lesions as stable when compared with the pretreatment size. EBV EBNA IgG, 1.4 (0–1.1); EBNA IgM (–); VCA IgM (–); VCA IgG, 10.6 (0–1.1); and 1 month later VCA IgG, 6 (0–1.1). The diagnosis of hepatitis B reactivation was established and chemotherapy was discontinued. After 2 months of follow-up his liver function tests were gradually normalized: ALT, 29 U/l; AST, 19 U/l; GGT, 37 U/l; ALP, 192 U/l; TB, 0.51 mg/dl; and HBV DNA, 10 pg/ml (normal value: 0–5 pg/ml).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
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Acute flares have been reported in cancer patients with chronic HBV infection under cytotoxic or immunosuppressive therapy. Clinically, reactivation ranges from mild transaminase increase to a fulminant course. Fatality up to 23% due to hepatic failure has been reported (3). Reactivation should be suspected when clinical hepatitis signs accompany abnormal liver function tests and increased HBV DNA level. Acute flares can also be induced by genotypic variation (precore mutant form, basal core promoter mutant form) or superinfection with other hepatotropic viruses or antiviral treatment, interferon, nucleoside analogue or corticosteroid withdrawal (1).
The incidence of hepatitis reactivation in HBsAg-positive cancer and lymphoma patients during chemotherapy was reported to be 44 and 67%, respectively, in two prospective studies (6,7). In these series, the etiology of hepatitis was found to be HBV reactivation in 44 and 72%, respectively. The identified risk factors for the acute exacerbation of HBV were male gender, younger age and lymphoma diagnosis (6,7). However, the presence of liver infiltration, baseline ALT, total bilirubin and HBV DNA levels were not found to be associated with HBV acute flare (6). Hepatotropic virus superinfection constitutes 20–30% of the etiology of acute flares in chronic HBV infection. Since serological tests were found to be negative, infection with another hepatotropic virus was also ruled out in the present case. Disease progression was ruled out by ultrasonography and computed tomography of the abdomen.
Our patient had five courses of chemotherapy including cisplatin and gemcitabine. Several chemotherapeutic agents including corticosteroids have been reported to be associated with the development of acute exacerbation of HBV in cancer patients (6,8). Anthracyclines and vinca alkaloids have been found to be associated with a higher incidence of HBV reactivation (6). Besides direct hepatotoxicity, immunosuppressive treatment such as chemotherapy, corticosteroids and transplant-related anti-rejection medications leads to enhanced viral replication in HBV carriers and when suppression is overwhelmed immune tolerance is broken and a rebound in host immune response leads to the destruction and necrosis of infected hepatocytes (1,9). Pinto et al. (10) reported five HBV carrier patients with lymphoproliferative malignancies, four of whom died after the cessation of chemotherapy including high-dose steroids.
In the present case, HBsAg was positive, HBeAg was negative, antiHBe was positive and HBV DNA was increased more than 45-fold. Unfortunately, the HBV DNA level before chemotherapy was not determined, which would have been helpful to confirm the effect on viral propagation. HDV, HCV and HAV IgM and IgG were found to be negative. Although reinfection with a mutant form cannot be completely ruled out, we considered the case as reactivation of hepatitis B. To clarify the reactivation of HBV mutants in HBeAg-negative patients, detection of mutants or HBV genome sequencing is needed, but in this case, we could not evaluate either of them. Up to now only a few cases of hepatitis B reactivation have been described in patients with solid tumors and, as far as we know, this is the first reported case of metastatic pancreas carcinoma with reactivation. Interferon has antiviral and immunomodulatory function and can be used in hepatitis B virus reactivation. Lamivudine is a nucleoside analogue that can be used for treating viral replication of hepatitis B virus reactivation. Response to the treatment can be seen with decreases in the levels of aminotransferases and HBV DNA within 3 months, and HBeAg seroconversion can be seen in 15–30% of patients in 1 year.
In HBsAg carrier patients, reactivation of hepatitis B between 14 and 72% has been reported (5,7). HBV-related complications cause delay or modification of treatment and the chance of cure decreases. There are no data to justify treating cancer patients with chronic HBV infection with less aggressive chemotherapy regimens. Even lamivudine, a nucleoside analogue that can be used for treating HBV replication, can cause acute flares of hepatitis within the first 4–6 weeks of therapy or upon withdrawal. Dienstag et al. (11) reported 3–10-fold increases from the baseline in 10% of HBV carrier patients during lamivudine therapy. Although prophylactic use of lamivudine deserves consideration in HBV carriers, there have been only a few studies on this approach (7,12) and optimum management of HBsAg-positive cancer patients remains to be elucidated.
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FOOTNOTES |
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+ For reprints and all correspondence: Berna Öksüzoglu, Simkent Sitesi 51 Sokak, 6 Blok, No. 26, 06610 Kirkkonaklar, Ankara, Turkey. E-mail: bernaoksuzoglu@hotmail.com
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REFERENCES |
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Received May 21, 2002; accepted September 9, 2002
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