Prospective study of hepatocellular carcinoma in nonalcoholic steatohepatitis in comparison with hepatocellular carcinoma cause by chronic hepatitis C

Department of Internal Medicine and Gastroenterology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
Journal of Gastroenterology (Impact Factor: 4.52). 04/2010; 45(9):960-7. DOI: 10.1007/s00535-010-0237-1
Source: PubMed


This study was performed to clarify the outcomes and recurrence of hepatocellular carcinoma (HCC) in nonalcoholic steatohepatitis (NASH) in comparison with the data for HCC caused by hepatitis C virus (HCV) infection.
Data for 34 NASH patients with HCC (NASH-HCC) were analyzed prospectively, and data for 56 age- and sex-matched patients with HCC due to HCV chronic liver disease (HCV-HCC) were collected retrospectively. After the initial treatment for HCC, patients were followed regularly at least every 4 months by performing clinical examinations, serum liver function tests, monitoring alpha-fetoprotein and des-gamma-carboxy prothrombin, and utilizing various imaging modalities.
The five-year survival rate was 55.2% and the cumulative recurrence of HCC at 5 years was 69.8% in treated cases of NASH-HCC. The NASH-HCC and HCV-HCC groups showed similar survival and recurrence rates. Of the 16 NASH-HCC patients curatively treated, recurrence was detected more than 2 years after the initial treatment in 9. Three patients showed intrahepatic recurrences away from the initial HCC, and 3 patients showed a change in tumor marker production after treatment of the initial HCC. The size of the HCC and the stage of fibrosis were significant risk factors for HCC recurrence in NASH-HCC.
HCC recurrence was very high in NASH, and the HCC may be of multicentric origin, similar to HCC based on viral hepatitis. Regular screening for HCC is extremely important for NASH patients with HCC, even after curative treatment. This study confirmed that NASH-HCC has a similar course to that of HCV-HCC.

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Available from: Katsutoshi Tokushige, Oct 29, 2015
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    • "Firstly, in this study, more than half of our patients had evidence of hepatitis B infection. This feature is distinctly different from countries where hepatitis C infection and NAFLD were the predominant etiologies of chronic liver disease [34]. Secondly, patients with hepatitis B or C might have received anti-viral treatment to suppress viral activity some time during the follow-up period, and this may alter the prognosis [35], [36]. "
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    ABSTRACT: The clinical aspects of cryptogenic hepatocellular carcinoma (HCC), defined as HCC in patients without hepatitis B, C or alcoholism, are not clear. We investigated its clinical presentations, long-term survival and prognostic predictors. A total of 2645 HCC patients were studied. One-to-one matched pairs between viral/alcoholic and cryptogenic HCC patients were generated by using the propensity model. The survival analysis was performed with the Kaplan-Meier method and log-rank test, and hazard ratios were calculated with Cox proportional hazards model. Among 366 (14%) patients with cryptogenic HCC, 34% of patients were presented with abdominal discomfort, and 31% of patients were identified incidentally. Compared to patients with viral/alcoholic HCC, cryptogenic HCC patients were significantly older (p<0.0001), with poorer performance status (p = 0.0031) and less often underwent curative treatment (p = 0.0041). They also had larger tumor burden (p<0.0001), poorer renal function (p<0.0001), lower α-fetoprotein level (p<0.0001), and more advanced Barcelona Clinic Liver Cancer stages (p<0.0001). With propensity score model, 366 pairs of similar HCC patients were selected and similar long-term survival between the two groups of patients was found (p = 0.1038). For cryptogenic HCC patients, α-fetoprotein ≧49 ng/mL (hazard ratio [HR]: 1.955, p = 0.0002), Child-Turcotte-Pugh class B/C (HR: 2.798, p<0.0001), performance status ≧1 (HR: 2.463, p<0.0001) and vascular invasion (HR: 1.608, p = 0.0257) were independent predictors of poor prognosis. Patients with cryptogenic HCC are usually diagnosed with poor general condition at late stages. However, cryptogenic HCC patients have similar prognostic predictors and long-term survival compared with viral/alcoholic HCC patients. Diagnosis at an early stage may improve their clinical outcomes.
    Full-text · Article · Feb 2014 · PLoS ONE
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    • "Single nodular presentation may be related to a lower tendency of portal vein invasion and, subsequently, less intrahepatic metastasis. Additionally, no significant difference was noted in Child Pugh classes, tumor stages, and overall survival rates between the cryptogenic HCC patients and the other HCC patients, a finding partially concordant with other reports [29-31]. In recent studies, patients with cryptogenic HCC had a higher survival rate than those with HCV-HCC and/or ALC-HCC after curative treatment [29,30]. "
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    ABSTRACT: Cryptogenic hepatocellular carcinoma (HCC) is thought to arise due to non-alcoholic fatty liver disease (NAFLD). This study investigated the prevalence, clinical features, and outcomes of cryptogenic HCC and compared them with those of HCC related to hepatitis B virus infection (HBV-HCC), hepatitis C virus infection (HCV-HCC), and alcohol (ALC-HCC) in Korea. The clinical features, treatment modalities, and survival data for 480 patients with HCC consecutively enrolled from January 2003 to June 2012 were analyzed. Computed tomography images were used to measure the visceral fat area (VFA) and liver-spleen density ratio. Cryptogenic HCC accounted for 6.8% of all HCC cases, whereas HBV-HCC, HCV-HCC, and ALC-HCC accounted for 62.7%, 13.5%, and 10.7% of HCC cases, respectively. The cryptogenic HCC group was characterized by older age, a low proportion of male patients, a high proportion of patients with metabolic syndrome or single nodular presentation, and a low proportion of patients with portal vein invasion compared to the viral-HCC and ALC-HCC groups. However, Child Pugh classes, tumor stages, and overall survival rates of cryptogenic HCC patients were similar to those of patients with HCC of other etiologies. VFA in cryptogenic HCC patients was significantly higher than that in viral-HCC patients, but similar to that in ALC-HCC patients. The liver-spleen density ratio did not vary according to HCC etiology. Cryptogenic HCC accounts for approximately 7% of HCC cases in Korea, associated with an older age at diagnosis, more frequent occurrence of metabolic syndrome, and less aggressive tumor characteristics, but similar survival compared to viral-HCC or ALC-HCC. Based on VFA and the liver-to-spleen density ratio, cryptogenic HCC may be burnt-out NAFLD in which visceral fat remains but liver fat is depleted.
    Full-text · Article · Jul 2013 · BMC Cancer
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    • "Tokushige et al. [18] "
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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.
    Full-text · Article · Sep 2012 · International Journal of Surgical Oncology
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