Nonalcoholic steatohepatitis-associated hepatocellular carcinoma: our case series and literature review

Department of Gastroenterology, Kurashiki Central Hospital, Okayama 710-8602, Japan.
World Journal of Gastroenterology (Impact Factor: 2.43). 03/2010; 16(12):1436-41.
Source: PubMed

ABSTRACT Recently, nonalcoholic steatohepatitis (NASH) has been considered to be another cause of liver cirrhosis and hepatocellular carcinoma (HCC). The natural history and prognosis of NASH are controversial. Accordingly, we assessed the clinicopathological features of NASH-associated HCC in our experience and reviewed the literature of NASH-associated HCC. We experienced 11 patients with NASH-associated HCC (6 male, 5 female; mean age 73.8 +/- 4.9 years) who received curative treatments. Most (91%) patients had been diagnosed with obesity, diabetes, hypertension, or dyslipidemia. Seven patients (64%) also had a non-cirrhotic liver. The recurrence-free survival rates at 1, 3 and 5 years were 72%, 60%, and 60%. We also summarized and reviewed 94 cases of NASH-associated HCC which were reported in the literature (64 male; mean age 66 years). The majority of patients (68%) were obese, 66% of patients had diabetes, and 24% had dyslipidemia. Furthermore, 26% of the HCCs arose from the non-cirrhotic liver. In conclusion, patients with non-cirrhotic NASH may be a high-risk group for HCC, and regular surveillance for HCC is necessary in non-cirrhotic NASH patients as well as cirrhotic patients.

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    • "Surprisingly, however , few clinical studies have been devoted to investigating NASH-associated HCC [1, 12–14] (Table 1). Similarly, few surgical series have been published [15] [16] [17] [18] [19] (Table 2). Of note, all papers describing partial liver resection for NASH- HCC originate from Japan. "
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    ABSTRACT: Introduction. Hepatocellular carcinoma is now known to arise in association with nonalcoholic steatohepatitis. The aim of this study is to examine the clinicopathological features of this entity using liver resection cases at a large Western center. Methods. We retrospectively reviewed all cases of partial liver resection for hepatocellular carcinoma over a 10-year period. We included for the purpose of this study patients with histological evidence of nonalcoholic steatohepatitis and excluded patients with other chronic liver diseases such as viral hepatitis and alcoholic liver disease. Results. We identified 9 cases in which malignancy developed against a parenchymal background of histologically-active nonalcoholic steatohepatitis. The median age at diagnosis was 58 (52-82) years, and 8 of the patients were male. Median body mass index was 30.2 (22.7-39.4) kg/m(2). Hypertension was present in 77.8% of the patients and diabetes mellitus, obesity, and hyperlipidemia in 66.7%, respectively. The background liver parenchyma was noncirrhotic in 44% of the cases. Average tumor diameter was 7.0 ± 4.8 cm. Three-fourths of the patients developed recurrence within two years of resection, and 5-year survival was 44%. Conclusion. Hepatocellular carcinoma may arise in the context of nonalcoholic steatohepatitis, often before cirrhosis has developed. Locally advanced tumors are typical, and long-term failure rate following resection is high.
    09/2012; 2012:915128. DOI:10.1155/2012/915128
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    • "F0-F2 Kawada et al., (Japan, 2009) [90] 6 M (3), F (3) Solitary F2-F3 Hashimoto et al., (Japan, 2009) [102] 4 n.r. Solitary (70%) F1-F2 Chagas et al., (Brazil, 2009) [111] 1 M (1) Multifocal F1 Takuma et al., (Japan, 2010) [33] "
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    ABSTRACT: Hepatocellular carcinoma (HCC) is a common cancer worldwide that primarily develops in cirrhosis resulting from chronic infection by hepatitis B virus and hepatitis C virus, alcoholic injury, and to a lesser extent from genetically determined disorders such as hemochromatosis. HCC has recently been linked to non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of obesity and related metabolic disorders such as diabetes. This association is alarming due to the globally high prevalence of these conditions and may contribute to the rising incidence of HCC witnessed in many industrialized countries. There is also evidence that NAFLD acts synergistically with other risk factors of HCC such as chronic hepatitis C and alcoholic liver injury. Moreover, HCC may complicate non-cirrhotic NAFLD with mild or absent fibrosis, greatly expanding the population potentially at higher risk. Major systemic and liver-specific molecular mechanisms involved include insulin resistance and hyperinsulinemia, increased TNF signaling pathways, and alterations in cellular lipid metabolism. These provide new targets for prevention, early recognition, and effective treatment of HCC associated with NAFLD. Indeed, both metformin and PPAR gamma agonists have been associated with lower risk and improved prognosis of HCC. This review summarizes current evidence as it pertains to the epidemiology, pathogenesis, and prevention of NAFLD-associated HCC.
    Journal of Hepatology 02/2012; 56(6):1384-91. DOI:10.1016/j.jhep.2011.10.027 · 10.40 Impact Factor
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    • "As with most cancers, hepatocarcinogenesis is a process attributed to progressive genomic changes that alter the hepatocellular phenotype producing cellular intermediates that evolve into HCC (Aravalli et al., 2008; Severi et al., 2010). The multistage process of tumor development in HCC that alter the hepatocellular phenotype includes steatosis, steatohepatitis and cirrhosis (Schutte et al., 2009; Takuma and Nouso, 2010). Therefore, we next sought to understand the pattern of ABCB6 expression during liver disease progression. "
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    ABSTRACT: ABCB6 is a mitochondrial transporter that regulates porphyrin biosynthesis. ABCB6 expression is upregulated in hepatocellular carcinoma (HCC) but the significance of this upregulation to HCC is not known. In the present study, we investigated: 1) ABCB6 expression in 18 resected human hepatocellular carcinoma (HCC) tissues and 3 human hepatoma cell lines; 2) pattern of ABCB6 expression during liver disease progression; and 3) functional significance of ABCB6 expression to HCC using the hepatoma cell line Huh7. ABCB6 expression was determined by real-time quantitative reverse transcription-polymerase chain reaction and western blotting. ABCB6 expression was upregulated in all the HCC specimens and the three-hepatoma cell lines. Increased ABCB6 expression correlated with liver disease progression with the pattern of expression being HCC > cirrhosis > steatosis. Small hairpin RNA (shRNA)-mediated knockdown of ABCB6 in Huh7 cells lead to decreased cellular proliferation and colony formation. Attenuation of ABCB6 expression did not affect Huh7 apoptosis but lead to a delay in G2/M phase of the cell cycle. In contrast, ABCB6 overexpression resulted in increased growth and proliferation of Huh7 cells. Since ABCB6 expression is induced in multiple tumor types we explored the role of ABCB6 in other cancer cells. ShRNA mediated knockdown of ABCB6 in HEK293 and K562 cells reduced cellular proliferation leading to a delay in G2/M phase, while ABCB6 overexpression promoted cell growth and proliferation. Collectively, these findings, obtained by loss of function and gain of function analysis, suggest that ABCB6 plays a role in cell growth and proliferation by targeting the cell cycle.
    Molecular oncology 07/2011; 5(5):410-25. DOI:10.1016/j.molonc.2011.07.005 · 5.94 Impact Factor
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