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H epatic resection and liver transplantation are aggressive, extirpative approaches to the treatment of selected patients for hepatocellular carcinoma (HCC) and are the only known potentially curative treatment options for this disease. Resection and transplantation are largely complimentary, not competing, treatments-resection for patients with preserved liver function and transplantation for patients with compromised liver function. Within each group, selection of patients for surgical therapy is currently based on morphologic criteria such as size, number of tumors, and degree of underlying liver disease.After resection, long-term survival can be expected in patients with solitary tumors regardless of size, especially when underlying fibrosis is minimal. 1 In fact, size has no significant impact on survival when microscopic vascular invasion is absent, as survival after resection of T1 tumors larger than 10 cm in diameter is similar to survival following resection of T1 tumors less than 5 cm. 1 Similarly, long-term survival can be expected when multiple tumors without vascular invasion are completely resected. 1 The establishment of strict morphologic criteria has significantly impacted the outcome after liver transplantation for HCC. Before the adoption of these criteria for transplantation, results with liver transplantation were poor. Recurrence rates ranged from 60% to 70%, 2,3 and the 5-year survival rate was less than 30%. 4,5 Since the implementation of more stringent selection criteria, survival rates after liver transplantation have been similar to those after resection for Abbreviations: HCC, hepatocellular carcinoma; AFP, alpha-fetoprotein; HR, hazard ratio; FNA, fine-needle aspiration.

BACKGROUND Advances in the diagnosis and surgical treatment of hepatocellular carcinoma (HCC) have improved the prognosis for patients with HCC who undergo liver resection. The objective of this study was to evaluate prognostic predictors for patients with HCC who underwent liver resection in a Japanese nationwide data base. METHODS In this study, the authors analyzed 12,118 patients with HCC in a Japanese nationwide data base who underwent liver resection between 1990 and 1999 and compared them with a previous analysis of patients between 1982 and 1989. All patients were evaluated for prognostic factors. RESULTS During the last decade, the increases in patients who were without hepatitis B virus surface antigen, who had small tumors, and who had portal vein invasion were noted. The 5‐year overall survival rates for patients with HCC improved to 50.5%, compared with < 40% in the previous analysis. A multivariate analysis using a stratified Cox proportional hazards model according to associated liver disease indicated that age, degree of liver damage, α‐fetoprotein level, maximal tumor dimension, number of tumors, intrahepatic extent of tumor, extrahepatic metastasis, portal vein invasion, hepatic vein invasion, surgical curability, and free surgical margins were independent prognostic predictors for patients with HCC. Operative mortality decreased from 2.3% in 1990–1991 to 0.6% in 1998–1999. CONCLUSIONS Outcomes and operative mortality rates in patients with HCC improved during the last decade. Age, degree of liver damage, α‐fetoprotein level, maximal tumor dimension, number of tumors, intrahepatic extent of tumor, extrahepatic metastasis, portal vein invasion, hepatic vein invasion, surgical curability, and free surgical margins were prognostic factors for patients with HCC who underwent liver resection. Cancer 2004. © 2004 American Cancer Society.

Uptake of Gd-EOB-DTPA in HCC is determined by expression of OATP1B3 rather than by tumor differentiation or bile production.

In the 17th Nationwide Follow-up Survey of Primary Liver Cancer in Japan, 18 213 individuals were newly registered as patients with primary liver cancer at 645 medical institutions over a period of 2 years (from 1 January 2002 to 31 December 2003). Of these patients, 94.2% had hepatocellular carcinoma (HCC) and 4.1% had intrahepatic cholangiocarcinoma (ICC). In addition, 24 705 follow-up patients were registered in the survey. Epidemiological and clinicopathological factors, diagnosis and treatment were investigated in the newly registered patients, and the cumulative survival rates of newly registered patients in the 12th to 17th follow-up surveys conducted between 1992 and 2003 were calculated for each histological type (HCC, ICC, and combined HCC and ICC) and stratified by background factors and treatment. The data obtained in this follow-up survey should contribute to future research and medical practice for primary liver cancer.

Aberrant DNA methylation is an important epigenetic alteration in hepatocellular carcinoma (HCC). However, the molecular processes underlying the methylator phenotype and the contribution of hepatitis viruses are poorly understood. The current study is a comprehensive methylation analysis of human liver tissue specimens. A total of 176 liver tissues, including 77 pairs of HCCs and matching noncancerous liver and 22 normal livers, were analyzed for methylation. Methylation of 19 epigenetic markers was quantified, and the results were correlated with different disease states and the presence or absence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. Based on methylation profiles, the 19 loci were categorized into 3 groups. Normal liver tissues showed methylation primarily in group 1 loci (HIC-1, CASP8, GSTP1, SOCS1, RASSF1A, p16, APC), which was significantly higher than group 2 (CDH1, RUNX3, RIZ1, SFRP2, MINT31) and group 3 markers (COX2, MINT1, CACNA1G, RASSF2, MINT2, Reprimo, DCC) (P < 0.0001). Noncancerous livers demonstrated increased methylation in both group 1 and group 2 loci. Methylation was significantly more abundant in HCV-positive livers compared with normal liver tissues. Conversely, HCC showed frequent methylation at each locus investigated in all 3 groups. However, the group 3 loci showed more dense and frequent methylation in HCV-positive cancers compared with both HBV-positive cancers and virus-negative cancers (P < 0.0001). Conclusion: Methylation in HCC is frequent but occurs in a gene-specific and disease-specific manner. Methylation profiling allowed us to determine that aberrant methylation is commonly present in normal aging livers, and sequentially progresses with advancing stages of chronic viral infection. Finally, our data provide evidence that HCV infection may accelerate the methylation process and suggests a continuum of increasing methylation with persistent viral infection and carcinogenesis in the liver. (HEPATOLOGY 2008;47:908-918.)

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