http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2013 , Hindawi Publishing Corporation . All rights reserved. Thu, 16 May 2013 10:20:57 +0000 http://www.hindawi.com/journals/ijhep/2013/802180/ Giant hepatic hemangiomas, though often asymptomatic, may require intervention if rapid growth occurs. The imaging studies including the computed tomography, magnetic resonance imaging, and ultrasonography, and so on are effective for the diagnosis and the management of this tumor; however, due to its size and various patterns of these studies, we need to carefully consider the therapeutic methods. Compared to the cost needed for these modalities, recently developed and approved Perflubutane- (Sonazoid-) based contrast agent enhanced ultrasonography is reasonable and safe. The major advantage is the real-time observation of the vascular structure and function of the Kupffer cells. By this procedure, we can carefully follow the tumor growth or character change in a hemangioma and decide the timing of therapeutic intervention, since abdominal pain, abdominal mass, consumptive coagulopathy, and hemangioma growth are the signs for the therapeutic intervention. We reviewed recent reports about Sonazoid-based enhancement and also showed the representative images collected in our department. This is the first review showing the detailed findings of the giant hemangiomas using Perflubutane (Sonazoid). This review will help the physician in making the decision, and we hope that Sonazoid will gain widespread acceptance in the near future. Masaki Maruyama, Osamu Isokawa, Koki Hoshiyama, Ayako Hoshiyama, Mari Hoshiyama, and Yoshihiro Hoshiyama Copyright © 2013 Masaki Maruyama et al. All rights reserved. Mon, 22 Apr 2013 14:15:32 +0000 http://www.hindawi.com/journals/ijhep/2013/875791/ Hepatitis B is a serious public health problem all around the world. It is a blood-borne and sexually transmitted DNA virus in adults, but mother to child transmission of hepatitis B virus also occurs in infants born to hepatitis B surface antigen positive mothers. Muhammad Umar, Hamama-tul-Bushra, Shifa Umar, and Haider Ali Khan Copyright © 2013 Muhammad Umar et al. All rights reserved. Thu, 18 Apr 2013 12:12:51 +0000 http://www.hindawi.com/journals/ijhep/2013/253261/ In Europe and North America, hepatocellular adenomas (HCA) occur, classically, in middle-aged woman taking oral contraceptives. Twenty percent of women, however, are not exposed to oral contraceptives; HCA can more rarely occur in men, children, and women over 65 years. HCA have been observed in many pathological conditions such as glycogenosis, familial adenomatous polyposis, MODY3, after male hormone administration, and in vascular diseases. Obesity is frequent particularly in inflammatory HCA. The background liver is often normal, but steatosis is a frequent finding particularly in inflammatory HCA. The diagnosis of HCA is more difficult when the background liver is fibrotic, notably in vascular diseases. HCA can be solitary, or multiple or in great number (adenomatosis). When nodules are multiple, they are usually of the same subtype. HNF1α-inactivated HCA occur almost exclusively in woman. The most important point of the classification is the identification of β-catenin mutated HCA, a strong argument to identify patients at risk of malignant transformation. Some HCA already present criteria indicating malignant transformation. When the whole nodule is a hepatocellular carcinoma, it is extremely difficult to prove that it is the consequence of a former HCA. It is occasionally difficult to identify HCA remodeled by necrosis or hemorrhage. Paulette Bioulac-Sage, Christine Sempoux, Laurent Possenti, Nora Frulio, Hervé Laumonier, Christophe Laurent, Laurence Chiche, Jean Frédéric Blanc, Jean Saric, Hervé Trillaud, Brigitte Le Bail, and Charles Balabaud Copyright © 2013 Paulette Bioulac-Sage et al. All rights reserved. Wed, 17 Apr 2013 18:12:16 +0000 http://www.hindawi.com/journals/ijhep/2013/141590/ Malignancy with liver metastasis plays an important role in daily oncology practice, especially for primary cancers of the gastrointestinal tract and hepatopancreatobiliary system. On account of the dual vascular supply system and the fact that most metastatic liver tumors are supplied by the hepatic artery, hepatic artery infusion chemotherapy (HAIC) is an appealing method for the treatment of liver metastases. Herein, we summarize recent study results reported in the literature regarding the use of HAIC for metastatic liver tumors, with special focus on colorectal cancer. Yi-Hsin Liang, Yu-Yun Shao, Jia-Yi Chen, Po-Chin Liang, Ann-Lii Cheng, and Zhong-Zhe Lin Copyright © 2013 Yi-Hsin Liang et al. All rights reserved. Sun, 14 Apr 2013 14:07:10 +0000 http://www.hindawi.com/journals/ijhep/2013/268625/ Focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) are benign hepatocellular tumors. The risk of bleeding and malignant transformation of HCA are strong arguments to differentiate HCA from FNH. Despite great progress that has been made in the differential radiological diagnosis of the 2 types of nodules, liver biopsy is sometimes necessary to separate the 2 entities. Identification of HCA subtypes using immunohistochemical techniques, namely, HNF1A-inactivated HCA (35–40%), inflammatory HCA (IHCA), and beta-catenin-mutated inflammatory HCA (b-IHCA) (50–55%), beta-catenin-activated HCA (5–10%), and unclassified HCA (10%) has greatly improved the diagnostic accuracy of benign hepatocellular nodules. If HCA malignant transformation occurs in all HCA subgroups, the risk is by far the highest in the β-catenin-mutated subgroups (b-HCA, b-IHCA). In the coming decade the management of HCA will be more dependent on the identification of HCA subtypes, particularly for smaller nodules (<5 cm) in terms of imaging, follow-up, and resection. Charles Balabaud, Wesal R. Al-Rabih, Pei-Jer Chen, Kimberley Evason, Linda Ferrell, Juan C. Hernandez-Prera, Shiu-Feng Huang, Thomas Longerich, Young Nyun Park, Alberto Quaglia, Peter Schirmacher, Christine Sempoux, Swan N. Thung, Michael Torbenson, Aileen Wee, Matthew M. Yeh, Shiou-Hwei Yeh, Brigitte Le Bail, Jessica Zucman-Rossi, and Paulette Bioulac-Sage Copyright © 2013 Charles Balabaud et al. All rights reserved. Tue, 09 Apr 2013 12:13:44 +0000 http://www.hindawi.com/journals/ijhep/2013/572307/ Colorectal cancer affects over one million people worldwide annually, with the liver being the most common site of metastatic spread. Adequate resection of hepatic metastases is the only chance for a cure in a subset of patients, and five-year survival increases to 35% with complete resection. Traditionally, computed tomographic imaging (CT) was utilized for staging and to evaluate metastases in the liver. Recently, the introduction of hepatobiliary contrast-enhanced magnetic resonance imaging (MRI) agents including gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Eovist in the United States, Primovist in Europe, or Gd-EOB-DTPA) has proved to be a sensitive method for detection of hepatic metastases. Accurate detection of liver metastases is critical for staging of colorectal cancer as well as preoperative planning. Kelly J. Lafaro, Panayota Roumanis, Aram N. Demirjian, Chandana Lall, and David K. Imagawa Copyright © 2013 Kelly J. Lafaro et al. All rights reserved. Thu, 04 Apr 2013 08:18:52 +0000 http://www.hindawi.com/journals/ijhep/2013/686420/ Aim. Chronic hepatitis C (CHepC) is frequently associated with hepatic iron overload, yet mechanisms underlying iron-induced liver injury have not been elucidated. We examined the significance of iron deposition in hepatocytes (HC) and reticuloendothelial cells (REC) in CHepC. Methods. Stainable hepatic iron was scored according to the iron deposition pattern in 373 patients. The levels of serum soluble TNF-α receptor (sTNFR2) and hepatic hepcidin mRNA and the efficacy of phlebotomy were compared among patients with different iron deposition patterns. Results. Serum transaminase levels and hepatic scores of stage, grade, and steatosis were higher in patients with REC iron staining than in those without. REC iron scores were independently associated with advanced stage. Serum sTNFR2 levels were significantly higher in patients with REC iron than in those without. REC iron scores were independently correlated with sTNFR2 levels. Compared with patients without stainable iron, those with iron overload had decreased ratios of hepcidin mRNA to serum ferritin. The efficacy of phlebotomy was greater in patients with REC iron than in those without REC iron. Conclusions. The present results show the importance of REC iron for the development of CHepC and the therapeutic effect of phlebotomy in CHepC. Hironori Mitsuyoshi, Kohichiroh Yasui, Kanji Yamaguchi, Masahito Minami, Takeshi Okanoue, and Yoshito Itoh Copyright © 2013 Hironori Mitsuyoshi et al. All rights reserved. Sun, 31 Mar 2013 18:35:14 +0000 http://www.hindawi.com/journals/ijhep/2013/434609/ Variceal hemorrhage is a common and devastating complication of portal hypertension and is a leading cause of death in patients with cirrhosis. The management of gastroesophageal varices has evolved over the last decade resulting in improved mortality and morbidity rates. Regarding the primary prevention of variceal hemorrhaging, nonselective β-blockers should be the first-line therapy in all patients with medium to large varices and in patients with small varices associated with high-risk features such as red wale marks and/or advanced cirrhosis. EVL should be offered in cases of intolerance or side effects to β-blockers, or for patients at high-risk for variceal bleeding who have medium or large varices with red wale marks or advanced liver cirrhosis. In acute bleeding, vasoactive agents should be initiated along with antibiotics followed by EVL or endoscopic sclerotherapy (if EVL is technically difficult) within the first 12 hours of presentation. Where available, terlipressin is the preferred agent because of its safety profile and it represents the only drug with a proven efficacy in improving survival. All patients surviving an episode of bleeding should undergo further prophylaxis to prevent rebleeding with EVL and nonselective β-blockers. Dong Hyun Kim and Jun Yong Park Copyright © 2013 Dong Hyun Kim and Jun Yong Park. All rights reserved. Sun, 31 Mar 2013 16:03:29 +0000 http://www.hindawi.com/journals/ijhep/2013/484903/ Liver involvement is often observed in several hematological disorders, resulting in abnormal liver function tests, abnormalities in liver imaging studies, or clinical symptoms presenting with hepatic manifestations. In hemolytic anemia, jaundice and hepatosplenomegaly are often seen mimicking liver diseases. In hematologic malignancies, malignant cells often infiltrate the liver and may demonstrate abnormal liver function test results accompanied by hepatosplenomegaly or formation of multiple nodules in the liver and/or spleen. These cases may further evolve into fulminant hepatic failure. Jun Murakami and Yukihiro Shimizu Copyright © 2013 Jun Murakami and Yukihiro Shimizu. All rights reserved. Sun, 31 Mar 2013 14:25:11 +0000 http://www.hindawi.com/journals/ijhep/2013/341636/ Under normal physiological conditions, the hepatocyte growth factor (HGF) and its receptor, the MET transmembrane tyrosine kinase (cMET), are involved in embryogenesis, morphogenesis, and wound healing. The HGF-cMET axis promotes cell survival, proliferation, migration, and invasion via modulation of epithelial-mesenchymal interactions. Hepatocellular cancer (HCC) is the third most common cause of worldwide cancer-related mortality; advanced disease is associated with a paucity of therapeutic options and a five-year survival rate of only 10%. Dysregulation of the HGF-cMET pathway is implicated in HCC carcinogenesis and progression through activation of multiple signaling pathways; therefore, cMET inhibition is a promising therapeutic strategy for HCC treatment. The authors review HGF-cMET structure and function in normal tissue and in HCC, cMET inhibition in HCC, and future strategies for biomarker identification. Neeta K. Venepalli and Laura Goff Copyright © 2013 Neeta K. Venepalli and Laura Goff. All rights reserved. Wed, 27 Mar 2013 10:58:23 +0000 http://www.hindawi.com/journals/ijhep/2013/374170/ Hepatocellular adenomas (HCAs) are currently categorized into distinct genetic and pathologic subtypes as follows: inflammatory hepatocellular adenoma, hepatocyte-nuclear-factor-1-alpha (HNF-1α-mutated) hepatocellular adenoma, and β-catenin-mutated hepatocellular adenomas; the fourth, defined as unclassified subtype, encompasses HCAs without any genetic abnormalities. This classification has accepted management implications due to different risks of haemorrhage and malignant transformation of the four subtypes. Imaging guided biopsy and/or surgical resection very important in obtaining definitive characterization; nevertheless, MRI with intra-extravascular and hepatobiliary (dual phase) agents, is an important tool not only in differential subtypes definition but even in surveillance with early identification of complications and discovery of some signs of HCA malignant degeneration. Inflammation, abnormal rich vascularisation, peliotic areas, and abundant fatty infiltration are pathologic findings differently present in the HCA subtypes and they may be detected by multiparametric MRI approach. Lesion enlargement and heterogeneity of signal intensity and of contrast enhancement are signs to be considered in malignant transformation. The purpose of this paper is to present the state of the art of MRI in the diagnosis of HCA and subtype characterization, with particular regard to morphologic and functional information available with dual phase contrast agents, and to discuss differential diagnosis with the most common benign and malignant lesions mimicking HCAs. Luigi Grazioli, Lucio Olivetti, Giancarlo Mazza, and Maria Pia Bondioni Copyright © 2013 Luigi Grazioli et al. All rights reserved. Mon, 11 Mar 2013 09:24:28 +0000 http://www.hindawi.com/journals/ijhep/2013/215064/ Benign liver tumors are very rare in children. Most focal nodular hyperplasia (FNH) remain sporadic, but predisposing factors exist, as follows: long-term cancer survivor (with an increasing incidence), portal deprivation in congenital or surgical portosystemic shunt. The aspect is atypical on imaging in two-thirds of cases. Biopsy of the tumor and the nontumoral liver is then required. Surgical resection will be discussed in the case of large tumors with or without symptoms. In the case of associated vascular disorder with portal deprivation, restoration of the portal flow will be discussed in the hope of seeing the involution of FNH. HepatoCellular Adenoma (HCA) is frequently associated with predisposing factors such as GSD type I and III, Fanconi anemia especially if androgen therapy is administered, CPSS, and SPSS. Adenomatosis has been reported in germline mutation of HNF1-α. Management will depend on the presence of a predisposing factor and may include metabolic control, androgen therapy withdrawn, or closure of the shunt when appropriate. Surgery is usually performed on large lesions. In the case of adenomatosis or multiple lesions, surgery will be adapted. Close followup is required in all cases. Stéphanie Franchi-Abella and Sophie Branchereau Copyright © 2013 Stéphanie Franchi-Abella and Sophie Branchereau. All rights reserved. Thu, 07 Mar 2013 09:37:09 +0000 http://www.hindawi.com/journals/ijhep/2013/314868/ Background and Aims. Chemotherapy of colorectal liver metastases can induce hepatotoxicity in noncancerous liver. We describe these lesions and assess risk factors and impacts on postresection morbidity and mortality in naive patients to chemotherapy before the era of bevacizumab. Methods. Noncancerous liver tissue lesions were analysed according to tumour, chemotherapy, surgery, and patient characteristics. Results. Fifty patients aged 62 ± 9.3 years were included between 2003 and 2007. Thirty-three (66%) received chemotherapy, with Folfox (58%), Folfiri (21%), LV5FU2 (12%), or Xelox (9%) regimens. Hepatotoxicity consisted of 18 (36%) cases of severe sinusoidal dilatation (SD), 13 (26%) portal fibrosis, 7 (14%) perisinusoidal fibrosis (PSF), 6 (12%) nodular regenerative hyperplasia (NRH), 2 (4%) steatosis >30%, zero steatohepatitis, and 16 (32%) surgical hepatitis. PSF was more frequent after chemotherapy (21% versus 0%, ), especially LV5FU2 (). SD was associated with oxaliplatin (54.5% versus 23.5%, ) and low body mass index (). NRH was associated with oxaliplatin () and extensive resection (). No impact on mortality and morbidity was observed, apart postoperative elevation of bilirubin levels in case of PSF (), longer hospitalization in case of surgical hepatitis (), and greater blood loss in case of portal fibrosis (). Conclusions. Chemotherapy of colorectal liver metastases induces sinusoidal dilatation related to oxaliplatin and perisinusoidal fibrosis related to 5FU, without any impact on postoperative mortality. Eric Nguyen-Khac, Céline Lobry, Denis Chatelain, David Fuks, Jean Paul Joly, Marie Brevet, Blaise Tramier, Charlotte Mouly, Vincent Hautefeuille, Bruno Chauffert, and Jean Marc Regimbeau Copyright © 2013 Eric Nguyen-Khac et al. All rights reserved. Thu, 28 Feb 2013 08:28:37 +0000 http://www.hindawi.com/journals/ijhep/2013/398308/ Light has been shed on the genotype/phenotype correlation in hepatocellular adenoma (HCA) recognizing HNF1α-inactivated HCA (H-HCA), inflammatory HCA (IHCA), and β-catenin-activated HCA (b-HCA). We reviewed retrospectively our surgical HCA series to learn how to recognize the different subtypes histopathologically and how to interpret adequately their immunohistochemical staining. From January 1992 to January 2012, 37 patients underwent surgical resection for HCA in our institution. Nine had H-HCA (25%) characterized by steatosis and loss of L-FABP expression; 20 had IHCA (55.5%) showing CRP and/or SAA expression, sinusoidal dilatation, and variable inflammation; and 1 patient had both H-HCA and IHCA. In 5 patients (14%), b-HCA with GS and β-catenin nuclear positivity was diagnosed, two already with hepatocellular carcinoma. Two cases (5.5%) remained unclassified. One of the b-HCA showed also the H-HCA histological and immunohistochemical characteristics suggesting a subgroup of β-catenin-activated/HNF1α-inactivated HCA, another b-HCA exhibited the IHCA histological and immunohistochemical characteristics suggesting a subgroup of β-catenin-activated/inflammatory HCA. Interestingly, three patients had underlying vascular abnormalities. Using the recently published criteria enabled us to classify histopathologically our retrospective HCA surgical series with accurate recognition of b-HCA for which we confirm the higher risk of malignant transformation. We also underlined the association between HCA and vascular abnormalities. S. Fonseca, D. Hoton, S. Dardenne, L. Annet, C. Hubert, S. Godecharles, A. Jouret-Mourin, R. Reding, J. B. Otte, J. Rahier, J. F. Gigot, and C. Sempoux Copyright © 2013 S. Fonseca et al. All rights reserved. Sun, 24 Feb 2013 16:07:09 +0000 http://www.hindawi.com/journals/ijhep/2013/604860/ Hepatocellular adenoma (HCA) is a benign neoplasm arising from hepatocytes. There is evidence that the inflammatory subtype may be associated with obesity and alcohol use and that men with metabolic syndrome may be at risk for malignant transformation of HCA. We sought to explore the combined experience of US centers as reported in the literature to document the epidemiologic shift in risk factors for HCA formation in the United States, namely, a shift from oral contraceptive pills (OCPs) to an emerging role of obesity as a contributing factor. Methods. Publications reporting HCA in the United States were identified through a PubMed search and a review of the literature. We excluded publications prior to 1970, single case reports, and publications for which there was no data available regarding patient characteristics including OCP use and the number of adenomas. Conclusion. Whereas earlier reports of HCA in the United States described cases exclusively in women exposed to OCPs, there is a trend towards an increase in HCAs reported in men, HCAs in the absence of OCP use, and increased reporting of multiple HCAs. This may be a result of newer OCP formulations and increasing prevalence of obesity. Charissa Y. Chang, Juan C. Hernandez-Prera, Sasan Roayaie, Myron Schwartz, and Swan N. Thung Copyright © 2013 Charissa Y. Chang et al. All rights reserved. Wed, 20 Feb 2013 14:32:28 +0000 http://www.hindawi.com/journals/ijhep/2013/103830/ Mammalian target of rapamycin (mTOR) and the microtubules are shown to be potential targets for treating hepatocellular carcinoma (HCC). PI3K/Akt/mTOR activation is associated with resistance to microtubule inhibitors. Here, we evaluated the antitumor activity by cotargeting of the mTOR (using allosteric mTOR inhibitor everolimus) and the microtubules (using novel microtubule-stabilizing agent patupilone) in HCC models. In vitro studies showed that either targeting mTOR signaling with everolimus or targeting microtubules with patupilone was able to suppress HCC cell growth in a dose-dependent manner. Cotargeting of the mTOR (by everolimus) and the microtubules (by patupilone, at low nM) resulted in enhanced growth inhibition in HCC cells (achieving maximal growth inhibition of 60–87%), demonstrating potent antitumor activity of this combination. In vivo studies showed that everolimus treatment alone for two weeks was able to inhibit the growth of Hep3B xenografts. Strikingly, the everolimus/patupilone combination induced a more significant antitumor activity. Mechanistic study demonstrated that this enhanced antitumor effect was accompanied by marked cell apoptosis induction and antiangiogenic activity, which were more significant than single-agent treatments. Our findings demonstrated that the everolimus/patupilone combination, which had potent antitumor activity, was a potential therapeutic strategy for HCC. Qian Zhou, Chi Hang Wong, Cecilia Pik Yuk Lau, Connie Wun Chun Hui, Vivian Wai Yan Lui, Stephen Lam Chan, and Winnie Yeo Copyright © 2013 Qian Zhou et al. All rights reserved. Wed, 20 Feb 2013 08:10:38 +0000 http://www.hindawi.com/journals/ijhep/2013/235040/ Introduction. The role of hepatic resection in patients with liver metastases from gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is still poorly defined. Therefore, we examined the results obtained with surgical resection and other locoregional or systemic therapies by reviewing the recent literature on this topic. We performed the meta-analysis for comparing surgical resection of hepatic metastases with other treatments. Materials and Methods. In this systematic review and meta-analysis of observational studies, the literature search was undertaken between 1990 and 2012 looking for studies evaluating the different survivals between patients treated with surgical resection of hepatic metastases and with other surgical or nonsurgical therapies. The studies were evaluated for quality, publication bias, and heterogeneity. Pooled hazard ratio (HR) estimates and 95% confidence intervals (CI.95) were calculated using fixed-effects model. Results. We selected six studies in the review, five of which were suitable for meta-analysis. We found a significant longer survival in patients treated with hepatic resection than embolisation HR 0.34 (CI.95 0.21–0.55) or all other nonsurgical treatments HR 0.45 (CI.95 0.34–0.60). Only one study compared surgical resection with liver transplantation and meta-analysis was not feasible. Conclusions. Our meta-analysis provides evidence supporting the hypothesis that hepatic resection increases overall survival in patients with liver metastases from GEP-NETs. Further randomized clinical trials are needed to confirm these findings and it would be desirable to identify new markers to properly select patients for surgical treatment. Stefano Bacchetti, Serena Bertozzi, Ambrogio P. Londero, Alessandro Uzzau, and Enrico Maria Pasqual Copyright © 2013 Stefano Bacchetti et al. All rights reserved. Tue, 19 Feb 2013 17:17:33 +0000 http://www.hindawi.com/journals/ijhep/2013/417323/ Immunohistochemistry is a valid method to classify hepatocellular adenoma (HCA). The aim was to test the performance of routine histology combined to glutamine synthetase (GS) staining to identify the 2 major HCA subtypes: HNF1α inactivated (H-HCA) and inflammatory HCA (IHCA). 114 surgical cases, previously classified by immunohistochemistry, were analysed. Group A comprised 45 H-HCAs, 44 IHCAs, and 9 β-catenin-activated IHCAs (b-IHCA), and group B, 16 b-HCA and unclassified HCA (UHCA). Steatosis was the hallmark of H-HCA. IHCA and b-IHCA were mainly characterized by inflammation, thick arteries, and sinusoidal dilatation; b-IHCA could not be differentiated from IHCA by routine histology. Group B was identified by default. A control set (91 cases) was analyzed using routine and GS stainings (without knowing immunohistochemical results). Among the 45 H-HCAs and 27 IHCAs, 40 and 24 were correctly classified, respectively. Among the 10 b-IHCAs, 4 were identified as such using additional GS. Eight of the 9 HCAs that were neither H-HCA nor IHCA were correctly classified. Conclusion. Routine histology allows to diagnose >85% of the 2 major HCA subtypes. GS is essential to identify b-HCA. This study demonstrates that a “palliative” diagnostic approach can be proposed, when the panel of specific antibodies is not available. Paulette Bioulac-Sage, Saïd Taouji, Brigitte Le Bail, Laurent Possenti, and Charles Balabaud Copyright © 2013 Paulette Bioulac-Sage et al. All rights reserved. Sun, 17 Feb 2013 08:04:26 +0000 http://www.hindawi.com/journals/ijhep/2013/827649/ Portal vein tumor thrombosis (PVTT) is a common complication of hepatocellular carcinoma (HCC) and has a negative impact on prognosis. This characteristic feature led to the rationale of the present trial designed to assess the efficacy and the safety of yttrium-90 glass-microsphere treatment for advanced-stage lobar HCC with ipsilateral PVTT. 18 patients with unresectable lobar HCC and ipsilateral PVTT were treated in our institution with 90Y-microS radioembolization. Patients were evaluated every 3 to 6 months for response, survival, and toxicity. Mean follow-up was 13.0 months (2.2–50.6). Outcomes were: complete response (), partial response (), stable disease (), and progressive disease () giving a disease control rate of 88.9%. Four patients were downstaged. Treating lobar hepatocellular carcinoma with ipsilateral portal vein thrombosis with yttrium-90 glass-microsphere radioembolization is safe and efficacious. Further clinical trials are warranted to confirm these results and to compare 90Y-microS with sorafenib, taking into account not only survival but also the possibility of secondary surgery for putative curative intention after downstaging. M. Pracht, J. Edeline, L. Lenoir, M. Latournerie, H. Mesbah, O. Audrain, Y. Rolland, B. Clément, J. L. Raoul, E. Garin, and E. Boucher Copyright © 2013 M. Pracht et al. All rights reserved. Tue, 15 Jan 2013 19:50:21 +0000 http://www.hindawi.com/journals/ijhep/2013/315947/ Hepatocellular adenomas (HCAs) are benign tumors developed in normal liver most frequently in women before menopause. HCAs lead to diagnostic pitfalls and several difficulties to assess the risk of malignant transformation in these young patients. Recent advances in basic knowledge have revealed a molecular classification related to risk factors, pathological features, and risk of transformation in hepatocellular carcinoma. Three major molecular pathways have been identified altered in specific HCA subgroups that are defined by either (1) inactivation of hepatocyte nuclear factor 1A (HNF1A) transcription factor, (2) activation of the WNT/β-catenin by CTNNB1 mutations, or (3) activation of the IL6/STAT3 pathway by somatic mutation of IL6ST, GNAS, or STAT3. Here, we will review the different molecular classes of HCA. Jean Charles Nault and Jessica Zucman Rossi Copyright © 2013 Jean Charles Nault and Jessica Zucman Rossi. All rights reserved. Wed, 26 Dec 2012 07:52:00 +0000 http://www.hindawi.com/journals/ijhep/2012/592354/ Pascal Loyer, Anne Corlu, and Chantal Desdouets Copyright © 2012 Pascal Loyer et al. All rights reserved. Mon, 24 Dec 2012 15:14:28 +0000 http://www.hindawi.com/journals/ijhep/2012/725735/ Because of the risk of hormone-induced growth and spontaneous rupture of hepatocellular adenoma (HCA) during pregnancy, special considerations are required. Due to the scarcity of cases, there is no evidence-based algorithm for the evaluation and management of HCA during pregnancy. We think it should be questioned if it is justified to discourage pregnancy in all women with HCA. The biological behavior of this benign lesion might be less threatening than presumed and a negative advice concerning pregnancy has great impact on the lives of these young female patients. The balance between the pros and cons of hepatic adenomas and pregnancy should be reconsidered. In our center, pregnancy in women with an HCA up to 5 cm is no longer discouraged in close consultation with the patient, her partner, and members of the liver expert team. Mirelle E. E. Bröker, Jan N. M. Ijzermans, Susanna M. van Aalten, Robert A. de Man, and Türkan Terkivatan Copyright © 2012 Mirelle E. E. Bröker et al. All rights reserved. Mon, 24 Dec 2012 14:34:10 +0000 http://www.hindawi.com/journals/ijhep/2012/870306/ Objective. Variation in the position of the liver between preablation and postablation CT images hampers assessment of treatment of colorectal liver metastasis (CRLM). The aim of this study was to test the hypothesis that discordant preablation and postablation imaging is associated with more ablation site recurrences (ASRs). Methods. Patients with CRLM were included. Index-tumor size, location, number, RFA approachs and ablative margins were obtained on CT scans. Preablation and postablation CT images were assigned a “Similarity of Positioning Score” (SiPS). A suitable cutoff was determined. Images were classified as identical (SiPS-id) or nonidentical (SiPS-diff). ASR was identified prospectively on follow-up imaging. Results. Forty-seven patients with 97 tumors underwent 64 RFA procedures (39 patients/63 tumors open RFA, 25 patients/34 tumours CT-targeted RFA, 12 patients underwent >1 RFA). Images of 52 (54%) ablation sites were classified as SiPS-id, 45 (46%) as SiPS-diff. Index-tumor size, tumor location and number, concomitant partial hepatectomy, and RFA approach did not influence the SiPS. ASR developed in 11/47 (23%) patients and 20/97 (21%) tumours. ASR occurred less frequently after open RFA than after CT targeted RFA (). ASR was associated with larger index-tumour size (18.9 versus 12.8 mm, ). Cox proportional hazard model confirmed SiPS-diff, index-tumour size >20 mm and CT-targeted RFA as independent risk factors for ASR. Conclusion. Variation in anatomical concordance between preablation and postablation images, index-tumor size, and a CT-targeted approach are risk factors for ASR in CRLM. Petra G. Kele, Eric J. Van der Jagt, Paul F. M. Krabbe, and Koert P. de Jong Copyright © 2012 Petra G. Kele et al. All rights reserved. Sun, 23 Dec 2012 13:26:28 +0000 http://www.hindawi.com/journals/ijhep/2012/410781/ Angiomyolipoma (AML) is a benign mesenchymal tumor that is frequently found in the kidney and, rarely, in the liver. The natural history of hepatic AML has not been clarified, and, because of the similar patterns in imaging studies, such as ultrasonography, computed tomography, and magnetic resonance imaging, some of these tumors have been overdiagnosed as hepatocellular carcinoma in the past. With an increase in the number of case reports showing detailed imaging studies and immunohistochemical staining of the tumor with human melanoma black-45, the diagnostic accuracy is also increasing. In this paper, we focused on the role of noninvasive imaging studies and histological diagnosis showing distinctive characteristics of this tumor. In addition, because several reports have described tumor progression in terms of size, recurrence after surgical resection, metastasis to other organs, and portal thrombosis, we summarized these cases for the management and discussed the indications for the surgical treatment of this tumor. Kenya Kamimura, Minoru Nomoto, and Yutaka Aoyagi Copyright © 2012 Kenya Kamimura et al. All rights reserved. Thu, 20 Dec 2012 10:25:13 +0000 http://www.hindawi.com/journals/ijhep/2012/429805/ Manuela Neuman, Nir Hilzenrat, Lawrence Cohen, Robert E. Winkler, and Radu Nanau Copyright © 2012 Manuela Neuman et al. All rights reserved. Mon, 17 Dec 2012 13:51:05 +0000 http://www.hindawi.com/journals/ijhep/2012/439024/ T helper 17 () is a novel subset of T helper cells that has recently been identified in the hepatocellular carcinoma (HCC) tumor environment. Its presence seems to be linked with HCC progression, possibly via facilitating angiogenesis. The origin of tumor-associated may be related to the gut, in which the differentiation of T cells, especially cells, is affected by microbiota. As may appear to be a new therapeutic target against tumor-promoting inflammation, strategies such as using probiotics to polarize the response away from may be beneficial to slow down tumor progression. This paper will attempt to discuss the potential linkage between HCC progression, , and gut microbiota and the possible therapeutic implications of probiotics to modulate -mediated response for tumor growth. Cecilia Ying Ju Sung, Nikki Pui-yue Lee, and Hani El-Nezami Copyright © 2012 Cecilia Ying Ju Sung et al. All rights reserved. Thu, 13 Dec 2012 08:30:45 +0000 http://www.hindawi.com/journals/ijhep/2012/937202/ Mario Reis Alvares-da-Silva, Heiner Wedemeyer, Helena Cortez-Pinto, and Claudia Pinto Marques Souza de Oliveira Copyright © 2012 Mario Reis Alvares-da-Silva et al. All rights reserved. Sun, 09 Dec 2012 09:36:39 +0000 http://www.hindawi.com/journals/ijhep/2012/950693/ Nonalcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are multidisciplinary liver diseases that often accompany type 2 diabetes or metabolic syndrome, which are characterized by insulin resistance. Therefore, effective treatment of type 2 diabetes and metabolic syndrome should target not only the cardiometabolic abnormalities, but also the associated liver disorders. In the last decade, it has been shown that metformin, thiazolidinediones, vitamin E, ezetimibe, n-3 polyunsaturated fatty acids, renin-angiotensin system (RAS) blockers, and antiobesity drugs may improve hepatic pathophysiological disorders as well as clinical parameters. Accordingly, insulin sensitizers, antioxidative agents, Niemann-Pick C1-like 1 (NPC1L1) inhibitors, RAS blockers, and drugs that target the central nervous system may represent candidate pharmacotherapies for NAFLD and possibly NASH. However, the efficacy, safety, and tolerability of long-term treatment (potentially for many years) with these drugs have not been fully established. Furthermore, clinical trials have not comprehensively examined the efficacy of lipid-lowering drugs (i.e., statins, fibrates, and NPC1L1 inhibitors) for the treatment of NAFLD. Although clinical evidence for RAS blockers and incretin-based agents (GLP-1 analogs and dipeptidyl peptidase-4 inhibitors) is also lacking, these agents are promising in terms of their insulin-sensitizing and anti-inflammatory effects without causing weight gain. Kei Nakajima Copyright © 2012 Kei Nakajima. All rights reserved. Sat, 01 Dec 2012 15:45:13 +0000 http://www.hindawi.com/journals/ijhep/2012/495950/ Previous studies have investigated extrahepatic multiple primary malignancy (EHPM) associated with hepatocellular carcinoma (HCC). However, its correlation with viral infection, such as hepatitis B virus (HBV) or hepatitis C virus (HCV), has not been examined. The aim of this study is to investigate the association between EHPM and hepatitis infection in HCC patients. A total of 412 patients who underwent surgical resection for primary HCC were enrolled. Viral infection was evaluated by serum HBV surface antigen (HBs Ag) and HCV antibody (HCV Ab). Sixty-eight (16.5%) patients had one or more EHPM. The most frequent EHPM was gastric cancer () in this cohort. No statistical significance was observed in the distribution of viral infection and incidence of entire EHPM. However, HCV Ab, HBs Ag, and negative status for both were correlated with the frequency of gastric (), urinary tract (), and breast cancer (), respectively. Infection of Helicobacter pylori was investigated by immunohistochemistry in gastric EHPM and resulted that 20 out of 21 analyzed cases were negative for Helicobacter pylori. Although it should be verified by well-designed large cohort studies, the current results suggested correlation between HCV infection and gastric cancer, HBV infection and urinary tract cancer and viral hepatitis-free status and breast cancer in HCC patients. Keita Kai, Atsushi Miyoshi, Kenji Kitahara, Masanori Masuda, Yukari Takase, Kohji Miyazaki, Hirokazu Noshiro, and Osamu Tokunaga Copyright © 2012 Keita Kai et al. All rights reserved. Tue, 27 Nov 2012 15:04:20 +0000 http://www.hindawi.com/journals/ijhep/2012/891516/ Metabolic syndrome (MS) is a cluster of metabolic derangements associated with insulin resistance and an increased risk of cardiovascular mortality. MS has become a major health concern worldwide and is considered to be the etiology of the current epidemic of diabetes and cardiovascular disease. In addition to cardiovascular disease, the presence of MS is also closely associated with other comorbidities including nonalcoholic fatty liver disease (NAFLD). The prevalence of MS in patients with cirrhosis and end-stage liver disease is not well established and difficult to ascertain. Following liver transplant, the prevalence of MS is estimated to be 44–58%. The main factors associated with posttransplant MS are posttransplant diabetes, obesity, dyslipidemia, and hypertension. In addition to developing NAFLD, posttransplant MS is associated with increased cardiovascular mortality that is 2.5 times that of the age- and sex-matched individuals. Additionally, the presence of posttransplant MS has been associated with rapid progression to fibrosis in individuals transplanted for HCV cirrhosis. There is an urgent need for well-designed prospective studies to fully delineate the natural history and risk factors associated with posttransplant MS. Until then, early recognition, prevention, and treatment of its components are vital in improving outcomes in liver transplant recipients. M. Shadab Siddiqui and Richard K. Sterling Copyright © 2012 M. Shadab Siddiqui and Richard K. Sterling. All rights reserved.