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Item Differentiating Hepatocellular Carcinoma from Hepatitis C Using Metabolite Profiling(MDPI, 2012-10-10) Wei, Siwei; Suryani, Yuliana; Gowda, G. A. Nagana; Skill, Nicholas; Maluccio, Mary; Raftery, Daniel; Surgery, School of MedicineHepatocellular carcinoma (HCC) accounts for most liver cancer cases worldwide. Contraction of the hepatitis C virus (HCV) is considered a major risk factor for liver cancer. In order to identify the risk of cancer, metabolic profiling of serum samples from patients with HCC (n=40) and HCV (n=22) was performed by 1H nuclear magnetic resonance spectroscopy. Multivariate statistical analysis showed a distinct separation of the two patient cohorts, indicating a distinct metabolic difference between HCC and HCV patient groups based on signals from lipids and other individual metabolites. Univariate analysis showed that three metabolites (choline, valine and creatinine) were significantly altered in HCC. A PLS-DA model based on these three metabolites showed a sensitivity of 80%, specificity of 71% and an area under the receiver operating curve of 0.83, outperforming the clinical marker alpha-fetoprotein (AFP). The robustness of the model was tested using Monte-Carlo cross validation (MCCV). This study showed that metabolite profiling could provide an alternative approach for HCC screening in HCV patients, many of whom have high risk for developing liver cancer.Item Infiltrative non-mass-like hepatocellular carcinoma initially presenting with isolated malignant portal vein thrombosis: A case report and review of the literature(Polish Ultrasound Society, 2020-03-31) Çolaklar, Anıl; Kemal Altınbaş, Namık; Radiology and Imaging Sciences, School of MedicineHepatocellular carcinoma (HCC) shows a rising incidence and mortality rates worldwide. HCC is divided into several distinct subtypes, both morphologically and histopathologically. Among these subtypes, infiltrative HCC may be the most challenging subtype to diagnose, given its characteristic myriad of tumor nodules blended with normal hepatocytes without a distinct mass-like lesion. Herein, we report an unusual case of an infiltrative HCC initially presenting with isolated malignant portal vein thrombosis and provide a brief review of the literature regarding the infiltrative HCC subtype. Additionally, we demonstrate how sonoelastography could aid in detecting the appropriate biopsy area in the infiltrative HCC subtype. To our knowledge, there have not been previously reported cases describing the use of sonoelastography in the evaluation of the appropriate area for the targeted liver biopsy.Item Letter to the Editor: Immortal time bias or sorafenib effect in elderly patients with HCC?(Wiley, 2017-08) Sanoff, Hanna K.; Chang, YunKyung; Lund, Jennifer L.; O'Neil, Bert H.; Dusetzina, Stacie B.; Department of Medicine, IU School of MedicineItem Nonsurgical Approaches to Treat Biliary Tract and Liver Tumors(Elsevier, 2019-10) Green, Benjamin L.; House, Michael G.; Surgery, School of MedicineEndoscopic and percutaneous therapies have been shown to prolong life and reduce morbidity for patients with unresectable advanced stages of primary hepatobiliary malignancies. This article reviews pertinent studies published within the last 5 years that involve locoregional techniques to manage hepatocellular carcinoma, perihilar and distal cholangiocarcinoma. A major emphasis is placed on photodynamic therapy, radiofrequency ablation, irreversible electroporation, and microwave ablation. Technical advances, combinational therapies, and postintervention outcomes are discussed. Despite widespread application, high-quality evidence does not show superiority of any particular locoregional technique for treating advanced hepatobiliary cancers.Item Optimal Timing of Administration of Direct-Acting Antivirals for Patients with Hepatitis C-Associated Hepatocellular Carcinoma Undergoing Liver Transplantation(Wolters Kluwer, 2021-10) Turgeon, Michael K.; Shah, Shimul A.; Delman, Aaron M.; Tran, Benjamin V.; Agopian, Vatche G.; Wedd, Joel P.; Magliocca, Joseph F.; Kim, Ahyoung; Cameron, Andrew; Olyaei, Ali; Orloff, Susan L.; Anderson, Matthew P.; Kubal, Chandrashekhar A.; Cannon, Robert M.; Locke, Jayme E.; Simpson, Mary A.; Akoad, Mohamed E.; Wongjirad, Chelsey P.; Emamaullee, Juliet; Moro, Amika; Aucejo, Federico; Feizpour, Cyrus A.; Vagefi, Parsia A.; Nguyen, Mindie H.; Esquivel, Carlos O.; Dhanireddy, Kiran; Subramanian, Vijay; Chavarriaga, Alejandro; Kazimi, Marwan M.; Anderson, Maia S.; Sonnenday, Christopher J.; Kim, Steven C.; Foley, David P.; Abdouljoud, Marwan; Salgia, Reena J.; Moris, Dimitrios; Sudan, Debra L.; Ganesh, Swaytha R.; Humar, Abhinav; Doyle, Majella; Chapman, William C.; Maithel, Shishir K.; Surgery, School of MedicineObjective: To investigate the optimal timing of direct acting antiviral (DAA) administration in patients with hepatitis C-associated hepatocellular carcinoma (HCC) undergoing liver transplantation (LT). Summary of Background Data: In patients with hepatitis C (HCV) associated HCC undergoing LT, the optimal timing of direct-acting antivirals (DAA) administration to achieve sustained virologic response (SVR) and improved oncologic outcomes remains a topic of much debate. Methods: The United States HCC LT Consortium (2015–2019) was reviewed for patients with primary HCV-associated HCC who underwent LT and received DAA therapy at 20 institutions. Primary outcomes were SVR and HCC recurrence-free survival (RFS). Results: Of 857 patients, 725 were within Milan criteria. SVR was associated with improved 5-year RFS (92% vs 77%, P < 0.01). Patients who received DAAs pre-LT, 0–3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 92%, and 82%, and 5-year RFS of 93%, 94%, and 87%, respectively. Among 427 HCV treatment-naïve patients (no previous interferon therapy), patients who achieved SVR with DAAs had improved 5-year RFS (93% vs 76%, P < 0.01). Patients who received DAAs pre-LT, 0–3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 93%, and 78% (P < 0.01) and 5-year RFS of 93%, 100%, and 83% (P = 0.01). Conclusions: The optimal timing of DAA therapy appears to be 0 to 3 months after LT for HCV-associated HCC, given increased rates of SVR and improved RFS. Delayed administration after transplant should be avoided. A prospective randomized controlled trial is warranted to validate these results.Item Sesn3 deficiency promotes carcinogen-induced hepatocellular carcinoma via regulation of the hedgehog pathway(Elsevier, 2019-10-01) Liu, Yunjian; Kim, Hyeong Geug; Dong, Edward; Dong, Chuanpeng; Huang, Menghao; Liu, Yunlong; Liangpunsakul, Suthat; Dong, Xiaocheng Charlie; Biochemistry and Molecular Biology, School of MedicineSestrin 3 (Sesn3) belongs to a small protein family that has been implicated in multiple biological processes including anti-oxidative stress, anti-aging, cell signaling, and metabolic homeostasis. However, the role of Sesn3 in hepatocellular carcinoma (HCC) remains unclear. Here we generated a Sesn3 knockout mouse model and induced HCC development by a combination of a single dose of diethylnitrosamine and chronic feeding of a choline deficient-high fat diet. After 6 months of the dietary treatment, Sesn3 knockout mice developed more severe HCC with higher levels of alpha-fetoprotein, arginase 1, and cytokeratin 19, but also higher metastatic rates than wild-type mice. Histological analysis revealed elevated extracellular matrix and cancer stem cell markers including Acta2, Cd44, and Cd133. Signaling analysis showed activated IL6-Stat3 and Akt pathways. Biochemical and microscopic analyses uncovered a novel inhibitory regulation of Gli2, a downstream transcription factor of the hedgehog signaling, by Sesn3. Two of the Gli2-regulated genes – Pdgfrb and Cd44 were upregulated in the Sesn3-deficient liver tissue. In conclusion, our data suggest that Sesn3 plays a critical tumor suppressor role in the liver partly through the inhibition of the hedgehog signaling.