Clinical Characteristics of NonBNonC- HCC: Comparison with HBV and HCV Related HCC

Abstract

Objective: To clarify the frequency and trends of both HBsAg and HCVAb negative hepatocellular carcinoma (NonBNonC-HCC) in all HCC, to clarify the etiology of NonBNonC-HCC, and to elucidate the clinical characteristics of NonBNonC-HCC compared with those of HBsAg-positive HCC (B-HCC) and HCVAb-positive HCC (C-HCC). Methods: A total of 2,542 patients with HCC examined at three institutions between 1991 and 2004 were categorized based on their serum viral antigen/antibody positivities, and compared between groups for the etiology, annual trend of the incidence, and clinical characteristics. Results: For the etiology, C-HCC was most prevalent, followed by B-HCC, NonBNonC-HCC, and both HBsAg and HCVAb-positive HCC (BC-HCC) in order. For survival, C-HCC had the most favorable prognosis, followed by NonBNonC-HCC, and B-HCC patients had the poorest prognosis in the three groups (C-HCC, B-HCC, and NonBNonC-HCC). In tumor-node metastasis (TNM) stages I+II, however, NonBNonC-HCC patients took the most favorable clinical course. The incidence of NonBNonC-HCC in all HCC was 5–8% from 1991 to 1998, and has increased to 10–12% since 1999. Additionally, the incidence of HBcAb-positive HCC in NonBNonC-HCC declined each year. Among NonBNonC-HCC patients, the morbidity of diabetic complications was significantly higher in HBcAb-negative patients than in HBcAb-positive patients. Conclusion: Although the incidence of NonBNonC-HCC among all HCC has an increasing trend recently, the incidence of HBcAb-positive HCC in NonBNonC-HCC has a tendency of decreasing. This fact suggest its etiology might be changing from occult HBV related HCC to unknown etiology such as nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) related HCC. The prognosis of NonBNonC-HCC was fairly good if the HCC was found in its early stage.

Metabolic risk factors are associated with non‐hepatitis B non‐hepatitis C hepatocellular carcinoma in Taiwan, an endemic area of chronic hepatitis B

“…Similarly, in Japan, an HCV‐endemic area, the proportion of NBNC‐HCC was 6.8%‐10% before 2000, but by 2009, this had increased to 17.3%‐19% 27, 28, 29, 30, 31, 32. A retrospective study by Tateishi et al28 revealed that the proportion of patients with HCC with nonviral etiologies increased from 10.0% in 1991 to 24.1% in 2010.…”

“…The category NBNC‐HCC indicated that a patient tested negative for all three viral markers: HBsAg, HBV DNA (undetectable), and anti‐HCV. In published reports, the diagnosis of NBNC‐HCC only required negative results for both HBsAg and anti‐HCV,27, 28, 29, 30, 31, 32, 33, 34 and tests for serum HBV DNA were not performed. In this study, we added HBV DNA criteria (undetectable) for the diagnosis of NBNC‐HCC because among the 2,153 patients with HBV‐HCC and the 310 patients with B+C‐HCC in our detailed viral marker study report, we identified 202 patients (8.20%) who tested negative for HBsAg but positive for HBV DNA 26.…”

Hepatitis B Virus Infection Is Associated with Poor Prognosis in Patients with Advanced Non Small Cell Lung Cancer

“…Subsequently, a large body of retrospective studies investigated the prognostic influence of HBV on cancer survival. HBsAg-positive hepatocellular carcinoma was found to have more unfavorable clinical course and worse survival than HBsAg-negative one (Hatanaka et al, 2007). Similarly, our study revealed that HBsAg-negative patients were significantly associated with favorable OS (12.56 months [12.23-12.89]) than HBsAg-positive counterpart (11.30 months [10.75-11.85]; p=0.001), and HBsAg-positive status remained as an independent unfavorable prognostic factor for OS by multivariate analysis (HR 0.740 [0.560,0.978], p=0.034).…”

“…It has been shown that that HBV reactivation is a welldescribed complication in hepatitis B surface antigen (HBsAg) positive cancer patients after chemotherapy, including advanced non small cell lung cancer (NSCLC), resulting in considerable morbidity and mortality (Yeo et al, 2006;Hoofnagle et al, 2009;Chen et al, 2012;Tang et al, 2013;Lin et al, 2014). In addition, HBV infection, as an independent prognostic factor, was demonstrated to confer poor survival in patients with pancreatic cancer and hepatocellular carcinoma (Hatanaka et al, 2007;Wei et al, 2013). However, the influence of HBV infection on prognosis in lung cancer patients is not well elucidated.…”

Fighting against viral hepatitis: Lessons from Taiwan

“…99 In Taiwan, I anticipate that nonalcoholic fatty liver disease, drug-induced liver injury, and several other biliary diseases will increase after the mid-21st century (Table 2). …”