Noncirrhotic hepatocellular carcinoma: etiology and occult hepatitis B virus infection in a hepatitis B virus-endemic area

Abstract

Background:Although hepatocellular carcinoma (HCC) usually develops in cirrhotic livers, a minority of cases occur in noncirrhotic livers (NCLs). We investigated etiology, clinicopathological features, and occult hepatitis B virus (HBV) infection (OBI) in patients with NCL HCC in an HBV-endemic area.Methods:A total of 710 patients who underwent resection or transplantation for HCC at the National Cancer Center (NCC), Korea, were enrolled. HCC and fibrosis stage were diagnosed pathologically.Results:A total of 178 patients (25%) did not have cirrhosis (NCL group). The main cause of HCC was HBV infection (77.2%), followed by cryptogenic disease (11.0%). The prevalence of NCL was 19.2%, 32.5%, 50.0%, and 48.7% among patients with HBV, hepatitis C virus (HCV), alcoholic, and cryptogenic disease, respectively (p < 0.05); corresponding nonfibrosis rates were 8.1%, 0%, 19.0%, and 24.3%, respectively. The NCL group was significantly older, with a larger tumor size, smaller tumor number, lower tumor stage, and more frequent non-HBV etiology. Among non-HBV HCC cases, 130 (80.2%) had antibodies against HBV core (HBc) and 55 (38.5%) had OBI. OBI-positive rates of 0%, 31.8%, and 52.6% were detected among HCV, alcoholic, and cryptogenic HCC cases, respectively. OBI did not correlate with advanced fibrosis. The NCL and liver cirrhosis (LC) groups did not differ in median overall survival.Conclusion:Regardless of etiology, a significant number of HCC patients, including half of nonviral cases, did not have LC. Half of cryptogenic HCC cases had OBI. This study promotes an understanding of fibrosis and OBI among patients with HCC in an HBV-endemic area.

Epidemiology of liver cancer in South Korea

“…Since Korea is a HBV-endemic area, prior HBV infection is considered to play a role even in the development of cryptogenic HCC [ 22 ]. A recent study reported that 82.1% of patients were positive for anti-HBc in serum and 52.6% were positive for both anti-HBc in serum and HBV DNA in the liver tissue among 78 patients who underwent resection or transplantation for cryptogenic HCC [ 23 ].…”

“…The prevalence of diabetes and obesity is increasing, and the age-standardized prevalences of diabetes and obesity (body mass index of 25 kg/m 2 or higher) in Korean adults were 11.0% and 31.8%, respectively [ 24 ]. Recent studies reported that diabetes was found in 21.8–37.1% of Korean patients with cryptogenic HCC [ 11 , 23 ]. It is of concern that nonalcoholic fatty liver disease-associated HCC can also develop in a non-cirrhotic liver [ 23 ].…”

“…Recent studies reported that diabetes was found in 21.8–37.1% of Korean patients with cryptogenic HCC [ 11 , 23 ]. It is of concern that nonalcoholic fatty liver disease-associated HCC can also develop in a non-cirrhotic liver [ 23 ]. Although a retrospective study showed that the proportion of HCC being based on nonalcoholic fatty liver disease without anti-HBc positivity increased from 3.8% in the years 2001–2005 to 12.2% in the years 2006–2010 [ 22 ], further studies are warranted.…”

Liver clear cell foci and viral infection are associated with non-cirrhotic, non-fibrolamellar hepatocellular carcinoma in young patients from South America

“…This situation implies that a significant fraction of Peruvian patients would have cryptogenic HCC, which is commonly characterized by a well-conserved architecture of the liver parenchyma and absence of a bona fide risk factor, such as overt HBV or HCV infections. It has been previously reported that occult HBV infection (OBI), defined by the presence of HBV DNA in blood or liver tissue without detectable levels of HBsAg, can be associated with non-cirrhotic HCC 44 . This is why we undertook a comprehensive molecular detection of HBV in tumor and non-tumor liver tissues.…”

Clinicopathologic characteristics and outcomes of hepatocellular carcinoma associated with chronic hepatitis B versus hepatitis C infection

“…The risk of HCC in HCV-infected individuals without cirrhosis has a prevalence of 16% to 30%. 43 , 44 The likelihood of HCC development in patients without advanced fibrosis may suggest the presence of other components in the pathological process of HCV that are not yet understood. 44 Several studies have documented a significant risk reduction for HCC when patients achieved sustained viral clearance with interferon treatment.…”