Hepatocellular adenomas (HCA) with activated ␤-catenin present a high risk of malignant transformation. To permit robust routine diagnosis to allow for HCA subtype classification, we searched new useful markers. We analyzed the expression of candidate genes by quantitative reverse transcription polymerase chain reaction QRT-PCR followed by immunohistochemistry to validate their specificity and sensitivity according to hepatocyte nuclear factor 1 alpha (HNF1␣) and ␤-catenin mutations as well as inflammatory phenotype. Quantitative RT-PCR showed that FABP1 (liver fatty acid binding protein) and UGT2B7 were downregulated in HNF1␣-inactivated HCA (P < 0.0002); GLUL (glutamine synthetase) and GPR49 overexpression were associated with ␤-catenin-activating mutations (P < 0.0005), and SAA2 (serum amyloid A2) and CRP (C-reactive protein) were upregulated in inflammatory HCA (P ‫؍‬ 0.0001). Immunohistochemistry validation confirmed that the absence of liver-fatty acid binding protein (L-FABP) expression rightly indicated HNF1␣ mutation (100% sensitivity and specificity), the combination of glutamine synthetase overexpression and nuclear ␤-catenin staining were excellent predictors of ␤-catenin-activating mutation (85% sensitivity, 100% specificity), and SAA hepatocytic staining was ideal to classify inflammatory HCA (91% sensitivity and specificity). Finally, a series of 93 HCA was unambiguously classified using our 4 validated immunohistochemical markers. Importantly, new associations were revealed for inflammatory HCA defined by SAA staining with frequent hemorrhages (P ‫؍‬ 0.003), telangiectatic phenotype (P < 0.001), high body mass index, and alcohol intake (P < 0.04). Previously described associations were confirmed and in particular the significant association between ␤-catenin-activated HCA and hepatocellular carcinomas (HCC) at diagnosis or during follow-up (P < 10 -5 ). Conclusion: We refined HCA classification and its phenotypic correlations, providing a routine test to classify hepatocellular adenomas using simple and robust immunohistochemistry. (HEPATOLOGY 2007;46:740-748.) H epatocellular adenomas (HCA) are rare benign liver tumors, most frequently occurring in women who are using oral contraception. Although HCA are mostly found as a single nodule, the presence of more than 10 in the liver indicates a specific nosological entity termed liver adenomatosis. 1 Two genetic alterations, the biallelic inactivation of hepatocyte nuclear factor 1 alpha (HNF1␣) and the activating mutation of ␤-catenin, have been described in HCA. 2,3 Recently, a comprehensive analysis of genetic, pathological, and clinical features in a series of 96 HCA enabled the identification of 4 HCA subtypes. 4 Biallelic HNF1␣ mutations defined the first group of HCA, phenotypically characterized by marked steatosis, lack of cytological abnormalities, and inflammatory infiltrates. Presence of a ␤-catenin-activating mutation defined the second group of HCA representing 15% of the cases generally characterized by a higher risk of malignant tr...

We took advantage of the reported genotype/phenotype classification to analyze our surgical series of hepatocellular adenoma (HCA). The series without specific known etiologies included 128 cases (116 women). The number of nodules varies from single, <5, and >5 in 78, 38, and 12 cases, respectively. The resection was complete in 95 cases. We identified 46 HNF1␣-inactivated HCAs (44 women), 63 inflammatory HCAs (IHCA, 53 women) of which nine were also ␤-catenin-activated, and seven ␤-catenin-activated HCAs (all women); six additional cases had no known phenotypic marker and six others could not be phenotypically analyzed. Twenty-three of 128 HCAs showed bleeding. No differences were observed in solitary or multiple tumors in terms of hemorrhagic manifestations between groups. In contrast, differences were observed between the two main groups. Steatosis (tumor), microadenomas (resected specimen), and additional benign nodules were more frequently observed in HNF1␣-inactivated HCAs (P < 0.01) than in IHCAs. Body mass index > 25, peliosis (tumor), and steatosis in background liver were more frequent in IHCA (P < 0.01). After complete resection, new HCAs in the centimetric range were more frequently found during follow-up (>1 year) in HNF1␣-inactivated HCA. After incomplete resection (HCA left in nonresected liver), the majority of HCA remained stable in the two main groups and even sometimes regressed. Six patients of 128 developed hepatocellular carcinoma (HCC) (all were ␤-catenin-activated, whether inflammatory or not). Conclusion: There were noticeable clinical differences between HNF1␣-inactivated HCA and IHCA; there was no increased risk of bleeding or HCC related to the number of HCAs; ␤-cateninactivated HCAs are at higher risk of HCC. As a consequence, we believe that management of HCA needs to be adapted to the phenotype of these tumors. (HEPATOLOGY 2009;50:481-489.)

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Although sarcopenia is a common complication of cirrhosis, its diagnosis remains nonconsensual: computed tomography (CT) scan determinations vary and no cutoff values have been established in cirrhotic populations undergoing liver transplantation (LT). Our aim was to compare the accuracy of the most widely used measurement techniques and to establish useful cutoffs in the setting of LT. From the 440 patients transplanted between January 2008 and May 2011 in our tertiary center, we selected 256 patients with cirrhosis for whom a recent CT scan was available during the 4 months prior to LT. We measured different muscle indexes: psoas muscle area (PMA), PMA normalized by height or body surface area (BSA), and the third lumbar vertebra skeletal muscle index (L3SMI). Receiver operating characteristic curves were evaluated and prognostic factors for post-LT 1-year survival were then analyzed. PMA offered better accuracy (area under the curve [AUC] = 0.753) than L3SMI (AUC = 0.707) and PMA/BSA (AUC = 0.732), and the same accuracy as PMA/squared height. So, for its accuracy and simplicity of use, the PMA index was used for the remainder of the analysis and to define sarcopenia. In men, the better cutoff value for PMA was 1561 mm (Se = 94%, Sp = 57%), whereas in women, it was 1464 mm (Se = 52%, Sp = 91%). A PMA lower than these values defined sarcopenia in patients with cirrhosis awaiting LT. One- and 5-year overall survival rates were significantly poorer in the sarcopenic group (n = 57) than in the nonsarcopenic group (n = 199), at 59% versus 94% and 54% versus 80%, respectively (P < 0.001). In conclusion, pre-LT PMA is a simple tool to assess sarcopenia. We established sex-specific cutoff values (1561 mm in men, 1464 mm in women) in a cirrhotic population and showed that 1-year survival was significantly poorer in sarcopenic patients. Liver Transplantation 23 143-154 2017 AASLD.