Hepatocellular carcinoma (HCC) is the fifth most frequently found primary malignant tumor in the world. Hepatic surgery and liver transplantation are considered optimal for the curative treatment of HCC. However, only 15-20% of HCCs may be surgically treated. Most of the surgically-non-eligible patients have to receive locoregional image-guided interventional treatments including intra-arterial and percutaneous ablative therapies. The goal of this paper is to review these interventional oncology approaches. Ablative therapeutic approaches include chemical therapies (such as ethanol or acetic acid injection), and thermal therapies (such as radiofrequency ablation, laser-induced thermotherapy, microwave ablation, cryoablation, and high-intensity focused ultrasound ablation). Catheter-based therapies include embolotherapy/chemotherapy-based treatments (such as transcatheter arterial chemoembolization, bland embolization, transcatheter arterial chemoinfusion, and chemoembolization with drug-eluting beads), and radiotherapy-based treatments (such as radioembolization with yttrium-90 and injection of iodine-131-labeled lipiodol). As a result of the technical development of locoregional approaches for HCC during the recent decades, the range of combined interventional therapies has been continuously extended. In this article, an evidence-based approach will be used to review the current role of interventional radiology therapies in the management of unresectable HCC.

Patients with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are at significant risk for hepatocellular carcinoma (HCC). The most important risk factor associated with HCC is liver cirrhosis, which is again predominantly caused by chronic HBV or HCV infection. The most effective approach to avoid HCC development is to prevent HBV and HCV infection through vaccination. Indeed, HBV vaccine is the first vaccine demonstrated to prevent cancers. However, a vaccine for HCV is not available. Thus, the prevention of HCV-related HCC and to a large extent HBV-related HCC (among persons who are already chronically infected) will rely on antiviral therapy to prevent progressive liver disease. The evidence that these patients can effectively be protected against HCC risk by the treatment with antiviral therapy is rather controversial, due to the lack of randomized controlled trials (RCTs) that are ideally needed to establish the effi cacy, but are logistically and ethically challenging. Although the strongest evidence to support that antiviral therapy can prevent HCC should be derived from RCTs with HCC as an endpoint, it should be emphasized that clinical trials showing the efficacy of antiviral therapy on virus suppression or eradication, and/or improvement in liver histology can be considered indirect evidence that antiviral therapy can prevent HCC because high virus levels (in the case of HBV infection) and cirrhosis (in both HBV and HCV infection) are the most important risk factors for HCC.

Aim: Epidermal growth factor (EGF) is a mitogen for hepatocyte grown in vitro, and its expression is up-regulated during liver regeneration. EGF also plays an important role in tumor initiation and progression. The goal of this study is to assess whether EGF is associated with advanced hepatocellular carcinoma (HCC) and also whether it is a predictive factor of shortened survival.

Methods: Serum EGF levels were evaluated in a total of 151 subjects: 51 patients with unresectable HCC, (21 of them were eligible for transarterial chemoembolization (TACE) and serum EGF levels were measured before and 1 week after TACE), 40 patients with chronic hepatitis without cirrhosis, 40 patients with cirrhosis, and 20 healthy controls. Patient demographic and laboratory variables were evaluated as predictive factors of survival in a Cox regression multivariate analysis using SPSS software.

Results: The mean serum level of EGF in patients with HCC was 784.49 pg/mL, which was significantly higher (P < 0.05) than all other groups. Mean EGF level in cirrhotic patients was 144.69 pg/mL; in those with chronic hepatitis C without cirrhosis, it was 338.64 pg/mL; and in healthy controls, it was 297.15 pg/mL. In group Ia patients who underwent TACE, the mean serum level of EGF was 759.76 ± 287.88 pg/mL before TACE, and 801.14 ± 276.12 pg/mL 1 week after treatment (P = 0.34). On multivariate Cox regression analysis only age (P = 0.03) and higher serum EGF level (P = 0.005), were inversely correlated with overall survival.

Conclusion: EGF levels were found to be significantly higher in HCC patients and together with age were the only predictors of poor survival in these patients. There was an increase in EGF levels 1 week after TACE in response to hypoxia; however, this increase was not statistically significant.

This article reports two patients with hepatocellular carcinoma (HCC) and type 2 diabetes mellitus (T2DM), who showed marked changes in hepatocellular glycogen content. Periodic acid-Schiff (PAS)-positive and diastase-PAS-negative (glycogen-storing) hepatocytes were detected in both background liver parenchyma and in HCC tissues. In HCC tissues, the number of glycogen-storing cells resembling hepatocytes was considerably reduced and unevenly distributed as compared with hepatocytes in background liver. To be known, changes in hepatocellular glycogen content in T2DM patients have not been previously described. It is hypothesized that the reduction in glycogen content in both patients was likely associated with the emergence of Warburg type of glycolysis.

Hepatocellular carcinoma (HCC) is one of the most common malignant cancers worldwide. However, the molecular mechanisms underlining the development and progression of HCC remain unclear. Genetic and genomic alterations are common events in various types of cancers including HCC. With the development and application of next generation sequencing technology, novel genetic and genomic alterations in HCC have been identified. Here, the article reviews recent updates on the genetic and genomic alterations in HCC.

Aim: Portal vein thrombosis (PVT) in the liver transplant recipient poses many challenges. Unfortunately, the risk factors and effects on outcomes of PVT are not well-defined.

Methods: This study analyzed the experience with PVT in liver transplant program from 2007 to 2013. This included the effectiveness of PVT diagnostics and its risk factors using logistical regression. The primary endpoints were Kaplan-Meir patient and graft survival. The secondary endpoints were the length of stay (LOS), transfusion rate, and overall morbidity. Independent predictors of survival were identified using a Cox’s proportional hazards model.

Results: Two hundred and sixteen consecutive liver transplant recipients were examined, and 30 (13.8%) had either a total or partial PVT. Two hundred and five patients had imaging within 1 year of liver transplantation with only 7 (23.3%) of the 30 PVTs identified pre-operatively. Calculated sensitivity (4.8-50%) and negative predictive values (10.5-22.2%) were poor. Only, age significantly predicted PVT [P = 0.037/hazard ratio (HR) =0.95]. Ninety-day-patient and graft survival for PVT was similar at 6 months, although 1-year survival was significantly lower. “Occult” PVT was not associated with inferior survival. Model for end-stage liver disease score > 25 (P = 0.001, HR = 0.49/P = 0.004, HR = 0.52) and age > 60 years (P = 0.017, HR = 0.64/P = 0.013, HR = 0.67) were significant predictors of patient and graft survival. Although the transfusion rate was significantly greater with PVT, LOS, and morbidity were not.

Conclusion: Older recipients had a greater likelihood of PVT. Diagnostic studies were not effective at excluding PVT, and occult diagnosis did not affect the outcome. PVT was not an independent predictor of mortality or graft loss, but was associated with greater blood loss but not increased LOS or morbidity.

Aim: Extracellular matrix (ECM)-adhesions and their interaction with actin cytoskeleton are fundamental for hepatocellular carcinoma (HCC). Fascin-1, an actin-bundling protein, is correlated with poor HCC prognosis, and is known regarding the molecular mechanism of its action. In this study, the authors investigated Fascin-1 basic molecular mechanism and cellular properties in HCC cells.

Methods: Fascin-1 was silenced by small interfering RNA and the expression of actin. The ECM-adhesion-related proteins were assessed along with the cells’ adhesion capacity in two cell lines that differ in terms of aggressiveness; the hepatoma cell line PLC/PRF/5 (Alexander) and the highly invasive HCC cell line HepG2.

Results: This study shows that Fascin-1 is upregulated in HepG2 cells compared to Alexander cells and when silenced leads to increased cell adhesion only in HepG2, while at the same time is associated with reduced migfilin and vasodilator-stimulated phosphoprotein (VASP) expression.

Conclusion: This is the first study to show that Fascin-1 contributes to a more aggressive phenotype in HCC cells and acts through migfilin and VASP.

Aim: To investigate the technique’s effectiveness and evaluate the risk factors affecting the success of “one-off” percutaneous ultrasound-guided radiofrequency ablation (RFA) for single hepatocellular carcinoma (HCC).

Methods: A total of 462 consecutive patients who received RFA from February 2010 to December 2013 at a single center (Eastern Hepatobiliary Surgery Hospital, Shanghai, China) were enrolled in the study. The patients were followed up for at least 6 months. Herein, this study adopted a new terminology named “one-off” ablation which is defined as achieving complete necrosis and no local residual or recurrent tumor within 6 months after single-session RFA. The incidence of “one-off” RFA was observed and the attributing risk factors were analyzed. A multivariate analysis was conducted to determine the independent predictive factors for the success of “one-off” ablation.

Results: The technique's effectiveness was 90.0% (416/462). After 6 months, 281 patients achieved "one-off" ablation, while 181 patients failed. On univariate analysis, tumor size ≤ 3 cm and tumor further from organs were found to be significantly correlated with "one-off" complete ablation (P = 0.003, and P = 0.010, respectively). On multivariate analysis using a logistic regression, tumor size ≤ 3 cm [odds ratio (OR), 0.534; 95% confidence interval (CI): 0.346-0.825, P = 0.005] and tumor further from organs (OR, 0.593; 95% CI: 0.387-0.909, P = 0.017) remained predictive.

Conclusion: Tumor size and tumor location are the predictive factors for the success of “one-off” ablation in patients with single HCC.

Hepatocellular carcinoma (HCC) is a common solid malignancy and a leading cause of cancer-related death worldwide. The mechanisms underlying the pathogenesis and development of HCC are complex and heterogeneous. Although mainly related to hepatitis B and C chronic infection; HCC may also arise from diet-associated conditions such as non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Furthermore, toxins and nutrients such as mycotoxins and alcohol have an established role in the pathogenesis of chronic liver diseases, whereas specific diet patterns or foods have been associated with a reduction in HCC risk. The aim of this review is to provide a thorough overview of the clinically relevant effects - either beneficial or detrimental - of natural products consumed by humans on HCC risk and management.

The molecular signalling pathways for hepatocellular carcinoma and hepatoblastoma have been extensively studied. The treatment of these highly vascular tumors mainly revolves around chemotherapy and surgery. Yet there is a high associated morbidity and mortality due to advanced stages, adverse effects owing to chemotherapy and recurrence. The role of Curcumin as an adjuvant remedy is explored in this article. Curcumin stimulates apoptosis of cancer cells, acts as anti-proliferative agent, has anti-angiogenic action, prevents tumor invasiveness and metastasis and prevents recurrence. It also has been proven to decrease the adverse effects of chemotherapeutic agents and has a synergistic anticancer action. It acts at the molecular level and affects the various metabolic pathways involved in tumorigenesis. It also promotes healing and has anti-inflammatory, anti-oxidant and anti-infective action. This natural phytocompounds has immense anti-cancer potential and holds future promise as an adjuvant remedy to treat liver cancer.

In the last decade, the incidence of hepatocellular carcinoma (HCC) is growing in both Europe and United States. Conventional therapies such as liver resection, transplantation, ablation, chemoembolization and sorafenib are not enough to avoid a significant mortality. Many studies suggested the positive effect of caffeine for prevention of HCC. Nevertheless, the amount of therapeutic caffeine and the high-dose safety are unknown. Many authors proposed Traditional Chinese Medicine as preventive and/or curative approach. Although it reveals limits such as the uncertain safety profile and the lack of evidence about a unique product, it shows interesting results in terms of survival and quality of life if given in combination with standard loco-regional therapy. Among the future promises, cannabinoids show interesting background mechanisms of blocking cell proliferation and neoangiogenesis. It is conceivable that in the next years, some natural products may have a role in improving the standards of care of HCC.

Aim: This study aimed to determine the composition of ethanol extract of jojoba seeds, and to evaluate its hepatoprotective effects in rats fed fumonisin B₁ (FB₁)-contaminated diet.

Methods: Jojoba seeds were extracted in 95% ethanol, and the chemical composition was determined. Male rats were divided into six groups and treated for 8 weeks as follows: (1) Untreated control; (2) FB₁-contaminated diet (80 mg/kg diet); (3) low dose (0.5 mg/kg b.w.) jojoba extract; (4) high dose (1.0 mg/kg b.w.) jojoba extract; (5) low dose jojoba extract plus FB₁; and (6) high dose jojoba extract plus FB₁. Blood and liver samples were collected for different biochemical analyses and histological examinations.

Results: The results indicated that the ethanolic extract of jojoba is rich in protein, phenolic compounds, phytic acid, and considerable amounts of simmondsin. Animals fed FB₁-contaminated diet showed severe biochemical and histological changes typical to those reported in literature. Treatment with jojoba seed extract alone at the two tested doses did not induce significant alterations in all parameters tested. Combined treatment of jojoba seed extract with FB₁ eliminated hepatotoxicity induced by FB₁, especially at low dose of jojoba seed extract.

Conclusion: The authors concluded that jojoba seed extract can be incorporated in FB₁-contaminated feed to eliminate FB₁-induced hepatotoxicity.

Aim: There are some previous reports concerning the relationship between prognosis of patients treated with sorafenib and parameters of computed tomography (CT) and magnetic resonance imaging (MRI). This study presents monocentric experience with sorafenib in the treatment of hepatocellular carcinoma (HCC) patients and will try to identify predictive factors for survival based on the correlation of results from imaging and survival.

Methods: A total of 38 HCC patients treated from April 2009 to December 2010 with sorafenib were included in this study. HCCs were classified as good arterial supply and poor arterial supply according to the enhancement intensity on CT scan or MRI. Clinical data were collected and survival time was analyzed by Kaplan-Meier method. A Cox’s regression model was performed to reveal predictive factors for survival.

Results: Among the 38 patients treated with sorafenib, mean age was 53.3 ± 11.1 years and 35 (92.1%) were males. Tumors in 17 patients were classified as good arterial supply, while the remaining 21 patients belonged to poor arterial supply. The median survival time (MST) was 10.7 months [95% confidence interval (CI), 8.7-12.7] and the 1-year overall survival (OS) was 41.0%. The MST and 1-year OS in patients with a good arterial supply of tumors were 12 months (range: 4-20 months) and 52.9%, compared with that of 7 months (range: 1-16 months) and 23.8% in patients with a poor arterial supply of tumors (P = 0.002). Patients who had tumors at Barcelona Clinic Liver Cancer (BCLC) stage B had longer MST and higher OS than those who had tumors at BCLC stage C, but there was no statistical difference between these two stages. On multivariate analysis, only arterial supply of the tumors remained statistically predictive for OS (hazard ratios 0.22, 95% CI, 0.07-0.67, P = 0.008).

Conclusion: Arterial blood supply is an independent predictor for survival in patients treated with sorafenib, and patients with a good arterial supply of tumors benefit more than those with a poor arterial supply of tumors.

Aim: The aim of this study is to prove or disprove the superiority of surgical resections over radiofrequency ablation (RFA) with respect to efficacy and safety.

Methods: The study was conducted in Zagazig University Hospitals, which included 40 patients with hepatocellular carcinoma (HCC) during the period from November 2011 to December 2014, using either liver resection or RFA.

Results: Hepatic resection was done in 20 patients (13 males, 7 females). Interventional RFA was done in 20 patients (12 males, 8 females). There was no in-hospital mortality after resection. One- and two-year survival rates were 85% and 70% respectively. There was no in-hospital mortality after RFA. One- and two-year survival rates were 80% and 65% respectively.

Conclusion: Surgical resection is preferred over RFA in HCC-liver cirrhosis Child A patients with tumor sizes ≥ 3 cm. HCC-liver cirrhosis Child A patients with masses < 3 cm have almost the same results with both surgery and RFA. But in special cases such as central position lesions, RFA is preferred over resection. Also the decision for management may be changed according to patients well. Surgical resection 1- and 2-year survival rates were better than those treated with RFA.

Malnutrition is almost universally present in patients undergoing liver transplantation. In this report, a male adult patient was followed from his pre-liver transplant phase until chronic post-transplant phase (3 months after the transplant). Improvement in nutrition status, quality of life, and performance status was seen from the pre-transplant to chronic post-transplant phase. Day to day nutrition monitoring and gradual increase in calorie and protein intake was seen in the acute post-transplant phase, but during pre- and chronic post-transplant phase, lack of nutrition support was observed in the patient.

This is a very interesting case of a 64-year-old female with a history of chronic hepatitis C infection, with abdominal pain and was found to have ruptured hepatocellular carcinoma (HCC). She was managed with the two-stage therapeutic approach first using transarterial embolization to provide adequate hemostasis and then surgical resection with an excellent outcome. This case report exemplifies the importance of early diagnosis and treatment of ruptured HCC.

Telomerase is a special reverse transcriptase, which adds telomeric DNA repeats to the ends of chromosome to offset loss. A vast majority of cancer cells have been shown that their telomerase was up-regulated and sustain proliferation and growth. Hepatocellular carcinoma (HCC) is one of the most commonly occurring cancers worldwide. It is also one of the leading causes of cancer death, and is connected with abnormal telomerase function. However, reports about the telomerase mutations and HCC are still insufficient. In this review, the structure and mechanism of action of telomerase, inherited disorders caused by its mutations, hepatocarcinoma, and drug development targeting telomerase are reviewed. However, further investigations are needed to elucidate human telomerase RNA gene regulation for initiation and progression of the liver cancer.

Hepatocellular carcinoma (HCC) has emerged as one of the most commonly diagnosed forms of human cancer; yet, the mechanisms underlying HCC progression remain unclear. Unlike other cancers, systematic chemotherapy is not effective for HCC patients, while surgical resection and liver transplantation are the most viable treatment options. Thus, identifying factors or pathways that suppress HCC progression would be crucial for advancing treatment strategies for HCC. The murine double minute 2 (MDM2)-p53 pathway is impaired in most of the cancer types, including HCC, and MDM2 is overexpressed in approximately 30% of HCC. Overexpression of MDM2 is reported to be well correlated with metastasis, drug resistance, and poor prognosis of multiple cancer types, including HCC. Importantly, these correlations are observed even when p53 is mutated. Indeed, p53-independent functions of overexpressed MDM2 in cancer progression have been suitably demonstrated. In this review article, we summarize potential effectors of MDM2 that promote or suppress cancer metastasis and specifically discuss the p53-independent roles of MDM2 in liver cancer metastasis from clinical as well as biological perspectives.

Aim: The liver is a sexually dimorphic organ presenting gender differences in its metabolism, functions, enzyme activity, membrane lipid composition and immune response. This paper aimed to assess whether gender may predict virological response to standard antiviral therapy in subjects with chronic hepatitis C (CHC).

Methods: The authors retrospectively analyzed 100 patients with genotype 1 CHC (55 men, 45 women), who performed standard antiviral therapy (interferon and ribavirin for 12 months) in the period 2002-2012, evaluated with blood tests and abdominal ultrasound to compare different virological and biochemical response in both gender.

Results: Rate of substained virological response (SVR) was higher, but not significant, in women than men (46.7% vs. 34.5%, P = 0.05); difference became significant after stratification by age (< 50 and ≥ 50 years). Specifically in the group aged under 50 years, rate of SVR was significantly higher in women than in men (66.7% vs. 38.2%, P < 0.05).

Conclusion: Female gender may predict virological response to standard antiviral therapy in subjects with CHC aged below 50 years. Considering new potent and more expensive antiviral drugs actually available for HCV treatment, it could be useful to identify candidates firstly eligible to therapy.

Cytokines are soluble extracellular small molecular weight protein or peptide. They are produced by virtually every nucleated cell type in response to injurious stimuli to control body metabolism, infection, inflammation and tissue or neuronal damage; therefore acting as messengers between tissues and the immune system; and participating in many physiological processes through their either anti-inflammatory or pro-inflammatory characteristics. Many cytokines have multiple cellular sources and targets, as well as many natural inducers and inhibitors. In pathophysiological conditions and during the early phase of chronic liver diseases, agent like virus, bacteria, parasites, ethanol, or toxins, induce secretion of cytokines at high levels. The presence of cytokine antagonists and soluble cytokine receptors, often released in concert with their respective cytokine agonist, presents additional complexity to interpretation.

Aim: The flowers of Bombax ceiba are traditionally used as home remedy in the treatment of jaundice and spleen enlargement. The present work investigated the effect of aqueous extract of flowers of Bombax ceiba (BCAE) on experimentally induced hepatotoxicity in rats to substantiate its traditional use as hepatoprotective agent.

Methods: Hepatotoxicity was induced in rats by carbon tetrachloride (CCl₄) treatment; at the same time vehicle or BCAE (250 or 500 mg/kg) or silymarin (25 mg/kg) were administered daily orally for seven days. Hepatotoxicity was assessed by estimating the activities of marker enzymes and by histological studies. The antioxidant effect of BCAE was assessed by measuring amount of antioxidant phytochemicals (total phenolics and flavonoids), and DPPH free radical scavenging assay of the extract.

Results: BCAE treatment significantly prevented the CCl₄-induced elevations in levels of glutamate oxaloacatate transaminase, glutamic pyruvic transaminase, alkaline phosphatase, bilirubin, and triglycerides, and decreased the total protein levels. Treatment with BCAE attenuated the CCl₄-induced cytotoxic damage to liver. BCAE exhibited presence of antioxidant phytochemicals and showed scavanging action on DPPH radicals. The hepatoprotective effect of BCAE was comparable to that of the standard antioxidant hepatoprotective agent, silymarin. These findings indicated that BCAE showed hepatoprotective effect against CCl₄-induced hepatotoxicity and exhibited in vitro antioxidant effects.

Conclusion: Bombax ceiba flowers exhibited hepatoprotective effect which may be attributed to antioxidant potential. This study also validated their traditional medicinal use in liver disorders.

Aim: Deregulation of microRNAs (miRNAs) expression has been identified in hepatocellular carcinoma (HCC), but few results are consistent. The objective of this study is to investigate “HCC tumor type specific” and “tumor common” miRNA panels.

Methods: The authors integrate and analyze clinical, etiologic and miRNA profiles data from 9 types of solid tumors in The Cancer Genome Atlas (TCGA) and HCC data from Columbia University Medical Center (CUMC).

Results: Levels of 33 miRNAs were significant different between HCC tumor and paired non-tumor tissues (over 2-fold changes) after Bonferroni correction for multiple comparisons, and most (28 miRNAs) were down-regulated in HCC tumors. Using this panel, the authors well classified HCC tumor tissues with 4 misclassifications among 48 paired tissues. Validating this panel in an additional 302 HCC tumor tissues, the authors almost perfectly distinguished tumor from non-tumor tissues with only two misclassifications (99% of HCC tissues correctly classified). Evaluating miRNA profiles in 32 independent HCC paired tissues from CUMC, the authors observed 40 miRNAs significantly deregulated in HCC with over 2-fold changes; 14 overlapped with those identified in TCGA. Subgroup analyses by HCC etiology found that 4 upregulated and 8 downregulated miRNAs were significantly associated with alcohol-related HCC. There were 7 and 4 miRNAs significantly associated with hepatitis B virus- and hepatitis C virus-related HCC, respectively. Data for the first time revealed that miR-24-1, miR-130a and miR-505 were significantly down-regulated only in HCC tumors; miR-142 and miR-455 were significantly down-regulated in HCC, but up-regulated in 5 other solid tumors; suggesting their HCC “tumor type specific” characteristics. A panel of 8 miRNAs was significant in at least 5 tumor types, including HCC, and was identified as “tumor common” marker.

Conclusion: The authors concluded that aberrant miRNA panels have HCC “tumor type specificity” and may be affected by etiologic factors.

As obligate intracellular parasites, viruses need a host cell to provide a milieu favorable to viral replication. Consequently, viruses often adopt mechanisms to subvert host cellular signaling processes. While beneficial for the viral replication cycle, virus-induced deregulation of host cellular signaling processes can be detrimental to host cell physiology and can lead to virus-associated pathogenesis, including, for oncogenic viruses, cell transformation and cancer progression. Included among these oncogenic viruses is the hepatitis B virus (HBV). Despite the availability of an HBV vaccine, 350-500 million people worldwide are chronically infected with HBV, and a significant number of these chronically infected individuals will develop hepatocellular carcinoma (HCC). Epidemiological studies indicate that chronic infection with HBV is the leading risk factor for the development of HCC. Globally, HCC is the second highest cause of cancer-associated deaths, underscoring the need for understanding mechanisms that regulate HBV replication and the development of HBV-associated HCC. HBV is the prototype member of the Hepadnaviridae family; members of this family of viruses have a narrow host range and predominately infect hepatocytes in their respective hosts. The extremely small and compact hepadnaviral genome, the unique arrangement of open reading frames, and a replication strategy utilizing reverse transcription of an RNA intermediate to generate the DNA genome are distinguishing features of the Hepadnaviridae. In this review, the authors provide a comprehensive description of HBV biology, summarize the model systems used for studying HBV infections, and highlight potential mechanisms that link a chronic HBV-infection to the development of HCC. For example, the HBV X protein (HBx), a key regulatory HBV protein that is important for HBV replication, is thought to play a cofactor role in the development of HBV-induced HCC, and the authors highlight the functions of HBx that may contribute to the development of HBV-associated HCC.

Aim: The present study was designed to evaluate the feasibility of preoperative liver functional volumetry performed by 3D-technetium-99m-diethylenetriaminepentaacetic acid-galactosyl-human serum albumin (^99mTc-GSA) scintigraphy/vascular fusion imaging using SYNAPSE VINCENT and to examine the discrepancy between conventional and functional volumetry.

Methods: The study group comprised 15 patients who underwent preoperative 3-dimensional (3D)-^99mTc-GSA scintigraphy/vascular fusion imaging using SYNAPSE VINCENT software before hepatectomy between July 2014 and August 2015. The diagnosis was hepatocellular carcinoma (n = 4), metastatic liver tumor (n = 10), or intrahepatic cholangiocarcinoma (n = 1). Right hepatectomy was performed in 2 patients, left hepatectomy in 3 patients, right posterior sectionectomy in 3 patients, segmentectomy in 2 patients, and partial hepatectomy in 4 patients. ^99mTc-GSA scintigraphy and computed tomography (CT) were performed to construct 3D-^99mTc-GSA scintigraphy/vascular fused images. The conventional volume ratio of the planned resection region without tumor (% CT), and the functional volume ratio of the planned resection region without tumor (% GSA) were calculated. The discrepancy ratio was calculated as follows: discrepancy ratio = 100 - % GSA/ % CT × 100 (%).

Results: The % GSA (17.9 ± 16.7%) was significantly lower than the % CT (21.5 ± 17.6%) (P < 0.036). In all except 2 patients, the % GSA was lower than the % CT. The discrepancy ratio ranged from -4% to 75% (median, 20.7%).

Conclusion: 3D-^99mTc-GSA scintigraphy/vascular fused images constructed using SYNAPSE VINCENT were useful for noninvasively performing functional liver volumetry in patients scheduled to undergo various patterns of hepatectomy. In planned resection regions without tumor, the functional volume ratio was about 20% lower than the conventional volume ratio.

Despite percutaneous laser thermal ablation (LTA) of liver tumors being regarded as a safe technique, major complications can occur. We report the first case of hemorrhagic cardiac tamponade after LTA of a colorectal metastasis in segment II of the liver. Unpredictable heat diffusion causing indirect thermal injury to the pericardium with resultant hemorrhagic reaction was hypothesized as the most likely cause of tamponade. A pericardial drain was emergently placed, 200 mL of bright red blood were drained, and the patient showed rapid hemodynamic improvement. For lesions located in segment II of the liver and strictly close to the pericardium, a careful risk/benefit analysis should be made by the multidisciplinary team to identify the best treatment option, taking into account both effectiveness and complications of each available technique.

Percutaneous hepatic perfusion (PHP) is an investigative technique for treating patients with diffuse unresectable metastatic liver disease. The technique has been clinically evaluated and shows great treatment potential for regional therapy to the liver. The advantage of PHP lies in its minimally invasive approach and ability to be repeated when compared to isolated hepatic perfusion. In a literature search, 135 publications were screened and 16 of these publications, including clinical trials and reviews, contributed to this review of PHP with melphalan. Melphalan is an alkylating agent that, when used as the chemotherapeutic agent in PHP, has shown potential for significant control of tumor burden in the liver, especially in metastatic ocular melanoma. In the current landscape of liver directed therapy, PHP is a viable option for those with unresectable metastatic disease to the liver. This article will focus on the technical aspects of PHP and describe the current data available from clinical trials, including outcomes of patients treated with this minimally invasive approach.

Zika virus infection is the present global problem. This arbovirus infection can cause acute illness and affect fetus in utero. However, there can be other additional clinical manifestation including to the hepatic disorder. In this short commentary article, the author briefly discusses on the liver problem due to Zika virus infection.

Malnutrition is universally prevalent among pre-liver transplantation patients. Malnutrition among cirrhotic patients had been associated to increased morbidity and mortality rates. Also, severely malnourished patients before the transplant surgery have a higher rate of complications and a decreased overall survival rate after liver transplantation. In light of the high incidence of malnutrition and associated complications, it is essential to initiate treatment as early as it is assessed. This review addresses the aetiologies of malnutrition and appropriate treatment strategies to correct it in pre-liver transplant phase. Treatment should focus on maintaining nutrient intake and correcting various nutritional deficiencies. The dietician plays an integral role as part of the transplant team by providing appropriate nutrition therapy for solving various nutrition problems.

Hepatocellular carcinoma (HCC) is a growing health problem in humans. HCC is considered the most common of internal malignancy which cause the death of human, but in the developed Western world, HCC is less common accompanied by increasing essentially in incidence, due to it occurs specially in chronic liver disease. HCC associated with various risk factors including hepatitis B virus infection; hepatitis C virus infection; prolonged aflatoxin exposure; and alcoholic cirrhosis. Overall, one-third of cirrhosis patients will develop HCC during their life time. Also, chemical carcinogens cause tumor promotions through free radical metabolites result in many biochemical and molecular changes that induces oxidative stress. The identify of HCC stage and underlying liver status then choosing the most appropriate line of therapy (surgical, loco regional, radiological and medical) can be improve the survival and/or the quality of life of the patient. Taken into the account of the nutritional value of some natural antioxidant agents that support the function of the body resulting an improvement of the health and protection from different diseases, our review will provide an up-dated status of the different aspects of HCC management through covering the efficacy and the beneficial effects of different natural agents and their mechanism of action against HCC for the future therapy modalities.

Aim: Hepatocellular carcinoma (HCC) is the fourth most common type of cancer and the third leading cause of cancer-related mortality. Sorafenib is an oral multikinase inhibitor that is used for unresectable advanced HCC. It is only approved systemic therapy for advanced HCC.

Methods: A retrospective prospective study conducted in a multispeciality hospital with 50 patients who received sorafenib. The primary outcome of the study was to find out the survival rate of patients treated with sorafenib. The secondary outcome of the study was to explore the efficacy and safety of sorafenib in a progression of HCC.

Results: The median overall survival in the Indian population was found as 114 days (3.8 months) after sorafenib therapy. The efficacy of the drug sorafenib was assessed by the survival days which were based on the changes in laboratory values such as haematological and clinical biochemistry. The adverse drug reaction documented in this study was vomiting, abdominal pain; fatigue; anorexia; hyperbilirubinemia; diarrhoea; hand-foot syndrome; rash; rectal bleeding; insomnia; constipation; thrombocytopenia and abdominal discomfort.

Conclusion: Sorafenib improves the overall survival of the patients with advanced HCC in Indian population up to 3.8 months. It is a safe and effective treatment for patients with advanced HCC in Indian population. The survival of patients was found to be depended on the liver function.

Aim: To evaluate the effectiveness of using cone-beam computed tomography (CBCT) in transcatheter arterial chemoembolization (TACE) to detect hapatocellular carcinoma (HCC) nodules and their feeding arteries.

Methods: Twenty-four patients with HCCs who underwent TACE using CBCT in addition to conventional digital subtraction angiography (DSA) were enrolled. After both conventional DSA and CBCT through the hepatic artery were acquired, TACE were performed. The nodules were defined as an HCC when dense accumulation of iodized oil was found within the nodule on CT obtained 2 weeks after the TACE. The number of detected nodules and identified feeding arteries, and their correlations with anatomical locations were assessed.

Results: A total of 39 HCC nodules (tumor diameter, 7-40 mm; mean, 17.4 ± 7.9 mm) were detected. Thirty-one nodules were detected by DSA alone but 8 nodules were additionally detected by adding CBCT to DSA. There were 53 feeding arteries associated with the 39 HCC nodules. Among these arteries, 21 were identified by DSA alone; however, 47 were identified by combining CBCT with DSA. Additional feeding arteries, especially for the nodules located at the right and caudate lobes, were identified by CBCT. On the other hand, there was no difference in detection of nodules between the anatomical locations by CBCT.

Conclusion: The use of CBCT in addition to DSA offers potential for increasing the number of detected nodules, and the number of their feeding arteries at the right and caudate lobes. CBCT might improve the quality of TACE procedure for HCC than DSA alone.

Liver resection is the preferred initial treatment option for solitary or limited multifocal hepatocellular carcinoma (HCC). However, because of the characteristics of HCC, including its high recurrence rate and the frequent presence of chronic hepatitis and cirrhosis, both curability and invasiveness must be considered when selecting a treatment for HCC. Laparoscopic liver resection (LLR) is minimally invasive and increasingly performed worldwide as a curative surgical option for treatment of liver tumors. The 2014 International Consensus Conference on LLR concluded that minor LLRs are now standard practice. Meta-analyses suggest that, as compared with open hepatectomy, LLR for patients with HCC, including those with cirrhosis, resulted in less blood loss, lower postoperative hospitalization rates, and similar oncological outcomes. Although candidates for this procedure should be carefully evaluated, LLR appears to be a feasible option for treatment of HCC with liver cirrhosis. This review describes the indications for LLR in this patient subgroup and offers guidance on appropriate surgical technique.

Aim: The adoption of laparoscopic liver resection has been expansive in the last 2 decades with the exception of cirrhotic patients. The current study examines the outcomes of our cirrhotic resections to determine the potential limitations of this technique.

Methods: Retrospective analysis of 114 cirrhotic patients. Seventy-five (65.8%) laparoscopic resections were compared to 39 open resections. Seventy-six (66.7%) resections in the series were minor resections (less than 3 segments). Surgical approach and extent of resection were analyzed using student’s t-test and regression multivariate analysis with SAS.

Results: The laparoscopic group had lower operative times (2.4 vs. 4.8 h; P < 0.001), blood loss (250 vs. 609 mL; P < 0.001), length of stay (4.4 vs. 10.1 days; P = 0.013) and complications (28% vs. 48%; P = 0.028). Subset analysis by technique and extent of resection identified the laparoscopic group lost the advantage in blood loss and lengths of stay when utilized in major resections. Multivariate regression analysis for blood loss further confirmed open resection (P = 0.014) and major resection (P = 0.026) as significant indicators of bleeding and transfusion.

Conclusion: Laparoscopic liver resection in cirrhotic patients is safe and efficacious. However, the significant variability in outcomes for major resections in cirrhotics leads us to recommend further examination of the learning curve and significant caution in the selection of cirrhotics requiring major hepatic resections.

A 73-year-old woman with liver cirrhosis caused by hepatitis C virus (HCV) underwent treatment of three hepatocellular carcinomas (HCCs) in liver segment 4, following three previous laparoscopic liver resections (LLRs) over 73 months. Contrast-enhanced computed tomography showed three 0.5-1.2 cm HCCs deep within the portal territories of subsegments 4a and 4b. The patient underwent laparoscopic resection of 4a and 4b, with the preservation of the portal branch to 4c, after minimal adhesiolysis around segment 4. The operation lasted 284 min, there was 50 mL of intra-operative bleeding and her recovery was uneventful. She was well, had experienced no recurrence and was HCV-negative, after taking oral anti-HCV therapy, 21 months later. LLR is associated with fewer adhesions after surgery and requires less adhesiolysis, because the laparoscope and forceps can be used in the small spaces between adhesions. The present patient underwent four LLRs over 6 years without severe deterioration of liver functional reserve. LLR is a useful localized therapy, which can be performed repeatedly and may prolong the survival of patients with multicentric metachronous HCCs.

Hepatocellular carcinoma (HCC) is a common malignant tumor and many cases occur in patients with liver cirrhosis. Although liver transplantation is the most effective treatment option, hepatectomy is still the first curative treatment option because liver transplantation is limited by the donors and high cost. In recent years, laparoscopic liver resection (LLR) has increasingly been performed in patients with liver cirrhosis, and has several advantages over open liver resection. Besides less pain and shorter hospital stay, LLR in patients with liver cirrhosis is also associated with lower incidences of postoperative liver failure and ascites because of greater preservation of collateral veins and less liver manipulation. With increasing experience, LLR for HCC located in segments 7 or 8 is now feasible, and anatomic LLR could be performed in patients with cirrhosis. Many comparative studies have shown that LLR is better than open liver resection in patients with liver cirrhosis in terms of a lower incidence of postoperative liver failure and similar patient survival. In conclusion, LLR is a promising treatment modality for HCC in patients with liver cirrhosis.

Aim: Laparoscopic liver resection for hepatocellular carcinoma (HCC) is increasingly common around the world. There may be significant advantages over open resections. However, due to technical difficulties, they are performed in few centers with expertise in liver and advanced laparoscopic surgery. In this study the authors summarize the experience to date.

Methods: A retrospective analysis of consecutive patients undergoing laparoscopic liver resection for HCC in 2 tertiary academic hepatobiliary units in Brisbane, Australia, between 1999 and 2015 was performed. Operative characteristics, perioperative morbidity, and pathological data were described. Patients with and without cirrhosis were analyzed and compared.

Results: Fifty-two patients underwent resection of 79 HCCs. Sixty-five percent of patients had cirrhosis. Fourteen percent of patients underwent a major hepatectomy. There was a trend towards more parenchyma-sparing resections for cirrhotic patients. Blood loss was higher in cirrhotics. Conversion to an open procedure occurred in 9%. There was one 90-day mortality due to liver failure (1.9%), and 7 patients (13%) experienced a complication. R0 resection was achieved in 92%. Overall survival at 1, 3, and 5 years was 88%, 81%, and 61%, respectively.

Conclusion: Laparoscopic liver resection for HCC, particularly in cirrhotic patients, is technically challenging. It can be performed with acceptable morbidity and adequate surgical margins.

Aim: The study was designed to assess the implications of enhanced recovery after surgery (ERAS) approach in patients submitted to open liver resection for hepatocellular carcinoma (HCC) comparing their short term outcome with patients treated by laparoscopic approach, in a case-matched design.

Methods: The open-group (n = 60) was matched in a ratio of 1:1 with patients undergoing laparoscopic liver resection for HCC (Lap-group, n = 60), with a matching achieved on a basis of propensity scores including 6 covariates representing patients characteristics and severity of the disease. Primary outcome analysis was performed in terms of ERAS-specific items and postoperative morbidity and mortality.

Results: Overall morbidity and mortality were comparable between groups. Incidence of ascites was slightly higher in the open- compared with the Lap-group (respectively 11.7% and 13.3%), without statistical significance. The need for introduction or increase of chronic diuretic therapy was significantly higher in the open-compared with the Lap-group (16.7% vs. 11.7%, P = 0.046). Furthermore, ascites more frequently required percutaneous drainage in the open-compared with the Lap-group (5% vs. 1.7% respectively, P = 0.041).

Conclusion: In patients who can’t benefit from minimally-invasive approach because of disease characteristics, ERAS management seems to be associated with an improved postoperative functional recovery and postoperative outcomes, comparable to those of the minimally invasive approach.

Aim: Transarterial embolization (TAE) has been found beneficial in treatment of ruptured Hepatocellular carcinoma (HCC) in earlier studies. So far no data is available from Pakistan. The aim of this study was to evaluate clinicopathological characteristics, outcomes of patients presented with spontaneously ruptured, unresectable HCC treated with or without TAE and to evaluate the factors associated with 30-day mortality.

Methods: This was a cross sectional study. Patients ≥ 18 years old, presented with spontaneous rupture of unresectable HCC, were evaluated. The outcome measures were control of bleeding, in-hospital mortality, 30-day mortality and factors associated with 30-days mortality.

Results: Out of 850 patients, 24 patients were diagnosed with spontaneously ruptured HCC. Mean age was 58.29 ± 15.26 years. A total of 11 (45.8%) patients were treated conservatively and 13 (54.2%) underwent TAE. Control of bleeding due to ruptured HCC was significantly higher for those treated via TAE as compared to those who were treated conservatively (92.3% vs. 36.4%, P = 0.008). Overall median duration for which the patients remained alive after HCC rupture was longer for TAE group (39 days vs. 5 days, P = 0.03). In-hospital mortality (30.8% vs.72.7%, P = 0.04) and 30-day mortality was also lower in TAE group (38.5% vs. 90.9%, P = 0.01). Those who underwent TAE had lower risk of mortality then conservative group [odds ratio (OR) 0.25, 95% confidence interval (CI) 0.07-0.90, P = 0.03). Failure to control bleeding was associated with higher 30-day mortality (OR 2.14, 95% CI 1.24-3.68, P = 0.009).

Conclusion: Ruptured HCC is a life threatening complication requiring early diagnosis and treatment. TAE is an effective and well-tolerated treatment in the management of ruptured HCC.

Hemophagocytic lymphohistiocytosis (HLH) is a cytokine storm syndrome caused by an overactive but ineffective immune reaction. Without prompt diagnosis and treatment, HLH is life-threatening. However, presenting symptoms are often nonspecific, with fatigue and fever being the most common. A high index of suspicion is therefore critical for early diagnosis and timely management. A previously healthy, 65-year-old female who initially presented with fever and abdominal pain developed abdominal compartment syndrome (ACS) requiring decompressive laparotomy on hospital day 6. Intraoperative frozen sections of biopsied liver showed intense portal lymphohistiocytic infiltrates. Epstein-Barr virus DNA copy numbers escalated from 600 copies/ mL after admission to 134,000 copies/mL before death. The diagnostic criteria of HLH-2004 were met. Patient expired on hospital day 12. It is important to raise awareness of ACS being an unusual presentation of HLH. Recent changes in diagnostic criteria tailored to adult HLH cases are reviewed.

Liver malignancies are the sixth leading cause of cancer worldwide, whereas hepatocellular carcinoma (HCC) is the most frequent histological type of liver cancer. Extrahepatic metastasis, which rarely involves the mediastinum, is associated with poor prognosis. An 80-year-old male presenting with mild diffuse abdominal pain for 4 months, associated with hyporexia, increased abdominal volume, dry cough, and loss of 4 kg in 1 month, sought medical assistance due to hemoptysis and chest pain. Tomographic study revealed HCC with mediastinal metastasis, after which sorafenib therapy was started. Disease progressed to death 4 months after the start of the treatment.

Despite doctors’ every effort to be vigilant when diagnosing, sometimes a preoperative diagnosis is disproved by postoperative pathological examination. A patient was diagnosed with hepatocellular carcinoma and received surgery as treatment. On operation, a solitary retroperitoneal mass rather than a liver lesion was seen. On histopathological examination, the retroperitoneal mass was found to be an extra-adrenal pheochromocytoma.

Histiocytic sarcoma is an uncommon non-Langerhans histiocyte disorder of mature tissue histiocytes. The authors presented an example of this rare tumor in a 14-year-old girl who presented with left upper quadrant pain, loss of appetite, and weight loss. A large 18 cm × 10 cm heterogeneous solid and cystic enhancing mass was found in the left lobe of the liver. Based on the histomorphology and positivity for histiocyte-specific markers in a needle biopsy, a diagnosis of histiocytic sarcoma was made. Chemotherapy was initiated, but the tumor did not respond well, and she died about 7 weeks following initial diagnosis with multi-organ failure. At autopsy, the tumor showed extensive necrosis, with no evidence of metastatic spread. In conclusion, the diagnosis of histiocytic sarcoma is challenging, and requires a high index of suspicion, with an appropriate panel of confirmatory immunohistochemical stains. Recognition of this rare tumor is important because of its poor response to chemotherapy and high mortality.

Aim: Dysregulated microRNAs (miRNAs) have been identified in hepatocellular carcinoma (HCC), but only a small proportion have been confirmed. An appropriate normalizer is crucial to determining the accuracy and reliability of data from miRNA studies.

Methods: Different normalization strategies were used to validate genome-wide miRNA profiles in HCC tumor and non-tumor tissues, and to determine the consistency and discrepancy of data on dysregulated miRNAs.

Results: Two sets of stable miRNAs (miR-30c/miR-30b and miR-30c/miR-126) were identified in HCC tissues by geNorm and NormFinder tools, respectively. The mean of global miRNAs also showed good stability for ranking the top 1-2 miRNAs, but the stabilities of the manufacturer-recommended ncRNAs controls were poor. Four panels of miRNAs were significantly associated with HCC by separately using various normalizers, and 14 miRNAs were consistently identified by three normalization strategies. Although fewer miRNAs (17-26) were dysregulated in HCC using the global mean or the 2 stable miRNAs as normalizers, perfect clustering of tissues was also obtained with only 1 to 2 misclassifications, suggesting the efficiency of the miRNA panels. Using global mean as the normalizer, the authors identified 7 miRNAs, including 2 novel (miR-324-5p and miR-550) significantly upregulated in HCC that were omitted when using 3 endogenous controls as the normalizer.

Conclusion: An optimal normalization strategy to identify biologically important miRNAs in HCC tissue studies of miRNA may be the combination of global mean and 2 stable miRNAs. Selection of appropriate normalization strategies to adjust miRNAs levels is particularly important for epidemiological studies dealing with large data sets and covering multiple experimental batches.

Aim: Early individualization of hepatocellular carcinoma is crucial to obtain good therapeutic results, thanks to several options such as percutaneous therapies, surgical resections and transplant. Aim of this study is to evaluate the vascularization of hepatocarcinoma using contrast enhanced ultrasound (CEUS) in comparison with multislice computed thomography (MSCT).

Methods: Between January 2009 and May 2014, 67 patients affected by hepatocarcinoma, who presented an overall of 92 nodules, were examined and enrolled in the study.

Results: There was a significant difference in the percentage of comparison of the vascularization between the nodules situated at a depth not greater than 9 cm, compared to those studied at a greater depth. In reference to the size of the lesion, the percentage of vascularization to the CEUS in arterial phase, compared with the MSCT, was 84% in lesions with dimensions equal or less than 1 cm, 91% in lesions with dimensions included between 1 and 2 cm, and 96% in the lesions greater than 2 cm.

Conclusion: CEUS is a method capable of documenting with very reliable accuracy the intralesional vascularization of hepatic carcinoma, in a superimposable manner to the MSCT. However, CEUS also presents some limitations, mainly in relation to the site of lesions.

Aim: Laparoscopic hepatectomy is increasing in utilization, however the procedure has not been adequately examined in the obese patient. This study aims to analyze the effect of obesity on perioperative outcomes after laparoscopic hepatectomy.

Methods: Retrospective analysis of 396 laparoscopic hepatectomies in normal [body mass index (BMI) < 25], overweight (BMI ≥ 25), obese (BMI ≥ 30), and severely obese (BMI ≥ 35) patients using multivariate regression models to determine the risk factors for post-operative complications.

Results: Normal BMI (n = 78; 20%), overweight (n = 209; 52%), obese (n = 86; 22%), and severely obese (n = 23; 6%). Demographics were similar except for a higher American Society of Anesthesiologists (ASA) score in the obese group. Estimated blood loss and operating time were greatest in the overweight group, while length of stay and complications were statistically similar between groups. Univariate analysis identified that complications were associated with weight class, ASA score, blood loss, and resection; multivariate analysis revealed ASA and transfusion were best correlated with complications.

Conclusion: Obese and overweight patients have similar complication profiles to normal BMI patients while severely obese patients have a higher incidence of complications that are primarily limited to Clavien-Dindo class I and II.

Hepatocellular carcinoma (HCC) is a common malignancy and an important cause of cancer death worldwide. Chronic hepatitis B virus (HBV) infection is the major cause of HCC. Recent studies of HBV-induced carcinogenesis not only discovered many new biomarkers but also developed a novel theory: Cancer Evolution-Development (Cancer Evo-Dev). Cancer Evo-Dev provides an evolutionary insight of developing more reasonable predictive and prognostic strategies. Characterizing chronic inflammatory microenvironment of cancer evolution, genetic polymorphisms of inflammatory factors, and HCC-related HBV mutations that negatively selected by host immunity may help greatly in identifying HBV-infected individuals who are more likely to develop HCC or benefit from HCC prophylactic options. Gene expression signatures and somatic mutation profiles reflect the different patterns of signaling pathway networks underlying tumor heterogeneity and can be applied to improve the molecular classification and prognostic stratification of HCC patients. Mutant cells that survive the selection can retro-differentiate into tumor initial cells and aggressive sub-clones. Detection of mutants or their hallmarks in cell-free DNA in peripheral blood potentially improve the early diagnosis, prognosis prediction, and personalized treatment of HBV-caused HCC.