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.

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.

A selection of patients with hepatocellular carcinoma (HCC) for surgical resection is crucial and algorithms/staging systems help surgeons to decide on a standard treatment for each patient and each HCC stage. However, there are always difficulties in remembering and/or recalling the contents of the algorithms/staging systems. Moreover, most algorithms/staging systems don’t include data about the extent of hepatectomy, intra-hepatic distribution of tumor(s), and technical feasibility of resection, all of which are vital in the surgeons’ decision-making process. Here, we aimed to present a simple and handy mnemonic acronym for selecting resectable HCCs in surgical practice. This was reproduced from the existing well-known staging systems. The designed mnemonic acronym is a phrase “PERISH” and it includes asking for Performance of patient, Extra-hepatic disease, Reserve of liver, Intra-hepatic distribution, Stratifying risk factors, and Hepatectomy size in order. Performance based on whether the patient is mostly bedridden or not, should be the first step of evaluation. Next, asking for suspicious metastasis as bone pain and radiological evaluation of abdomen/thorax is mandatory. The calculation of Child-Pugh score is only the third step. Good candidates for surgical resection should be Child-Pugh “A” with normal bilirubin levels. Technical feasibility of resection according to the intra-hepatic distribution of tumor(s) should be done later and the candidates preferably should not have portal hypertension (no splenomegaly, no thrombocytopenia). If the patient fulfils all the previous steps, the surgeon may perform indo-cyanine green clearance test. Consequently, following the PERISH flowchart may prevent “perish” of the surgeons while selecting the appropriate resectable HCCs.

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.

Hepatocellular carcinoma (HCC) arising in non-cirrhotic livers is relatively rare. Compared with HCC arising in cirrhotic livers they have some quirks. HCC in healthy livers are large tumors at diagnosis, and are detected due to the onset of abdominal symptoms, outside of any scheduled monitoring program. In non-cirrhotic patients, HCC has the same appearance as the classic image of cirrhotic HCC substrate. The presence of capsule, extensive intratumoral necrosis and typical behavior in the dynamic study after administration of intravenous contrast are present in most of the non-cirrhotic livers. In the presence of a suspicious lesion of HCC, we must assess the existence of underlying chronic liver disease. Ultrasound, computed tomography, and conventional magnetic resonance are imaging techniques that have a high specificity for the diagnosis of cirrhosis, but exhibit low sensitivity for diagnosis in the early stages of the disease. In recent years, new imaging methods are being developed to assess emerging liver fibrosis. In particular, in patients without chronic liver disease it is imperative to consider the differential diagnosis with other tumors that may settle in healthy livers with similar radiological characteristics as HCC. Therefore, in the presence of a lesion with pathognomonic radiological characteristics of HCC in the absence of cirrhosis, biopsy is required.

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.

Systemic therapy for hepatocellular carcinoma (HCC) has been disappointing. The only drug approved by Food and Drug Administration recently has been sorafenib. Sorafenib has modest benefits with a low response rate and an improvement in time to progression of only 2-3 months. Multiple randomized trials, which compare the new agent to sorafenib as either first line or second line therapy, have been negative, showing no improved clinical benefit. Recently, in a large phase III randomized trial, regorafenib has shown superiority to placebo as a second line treatment for HCC. However, this drug has multiple side effects and is not well tolerated by many patients. The clinical benefit is also modest. Clearly, new approaches to treat advanced HCC are still needed. There is data showing that HCC is immunogenic and the immune system can be stimulated to attack these cancer cells. This article will briefly review immunotherapy as a promising treatment for HCC.

Over the past few years, despite improvement in screening and diagnosis of hepatocellular carcinoma (HCC), advanced stage remains the most common presentation at diagnosis, with limited management options, especially options available to patients in limited resource countries. There is currently no effective systemic chemotherapy, targeted, or immunologic therapy for advanced stage HCC. Sorafenib is the only approved front-line molecular-targeted treatment,with slight survival benefit. Regorafenib has recently been approved as second line therapy for HCC after failure of sorafenib. Ongoing research on molecular agents targeting different pathways, combination therapies, and immunotherapy, represent hope for new treatment modalities. This manuscript reviews current treatment, ongoing research, and potential future treatments for advanced HCC.

Hepatorenal syndrome is not an uncommon life-threatening complication arising from liver cirrhosis. The diagnostic criteria for this syndrome have been revised throughout the years, with recent revisions aimed at improving earlier diagnosis and treatment. Liver transplantation remains the only definitive treatment for hepatorenal syndrome. Due to the scarcity of liver grafts, many patients die waiting. This review focuses on the different strategies to bridge patients to liver transplantation and to improve the postoperative outcome.

Liver diseases are most common disorders in the world and characterized by rapid changes from steatosis to chronic hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Natural products that attained great attention is to be used in the prevention and treatment of multiple diseases in humans. Several researches have been reported numerous natural and phytochemical compounds that may counteract or prevent the hepatic injury and primary liver cancer. The conservative treatment of liver toxicity and HCC may face awkward challenges in chemotherapy such as therapeutic failure or drug resistance. Accordingly, there is an actual need for safe and effective therapeutic and preventive modalities for liver disorders. The present review aims to focus on the potential protective and therapeutic effects of natural compounds in prevention and treatment of hepatotoxicity and HCC. It also demonstrates the mechanism of the natural products in enzymatic regulation of antioxidants and its role in apoptosis and proliferation of cancerous lesions of hepatocytes. Accordingly, it highlights the promising role of natural bioactive compounds and provides the rational for further transitional researches, and emphasize on the scientific validation of natural compounds for therapeutic portfolio for clinical use in liver diseases.

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.

Systemic therapy for hepatocellular carcinoma (HCC) has been disappointing. The only drug approved by Food and Drug Administration recently has been sorafenib. Sorafenib has modest benefits with a low response rate and an improvement in time to progression of only 2-3 months. Multiple randomized trials, which compare the new agent to sorafenib as either first line or second line therapy, have been negative, showing no improved clinical benefit. Recently, in a large phase III randomized trial, regorafenib has shown superiority to placebo as a second line treatment for HCC. However, this drug has multiple side effects and is not well tolerated by many patients. The clinical benefit is also modest. Clearly, new approaches to treat advanced HCC are still needed. There is data showing that HCC is immunogenic and the immune system can be stimulated to attack these cancer cells. This article will briefly review immunotherapy as a promising treatment for HCC.

Worldwide, hepatocellular carcinoma (HCC) is a significant cause of morbidity and mortality. In men, it is the fifth most common cancer and seventh most common in women; HCC is the second highest cause of cancer-related death worldwide. It is less prevalent in the USA and Northern Europe and more prevalent in Eastern and South-Eastern Asia. Over 700,000 cases are diagnosed each year - half of which occur in China - and result in roughly the same number of deaths per year. HCC significantly impairs quality of life and is associated with great costs to society. It is estimated that half of the deaths from HCC are associated with hepatitis B virus (HBV). Fortunately, HBV vaccination and antiviral therapy have shown excellent efficacy in decreasing the incidence of HCC. We will discuss the relationship of HBV to HCC, address available treatments for HBV and the impact of treatment on the development of HCC.

In Hong Kong, surgical resection is the core curative treatment for huge and advanced hepatocellular carcinoma (HCC). For tumors measuring 10 cm or above, major hepatectomy is usually required, but a future liver remnant not large enough will preclude the operation. Hypertrophy of future liver remnant is a way to render more patients operable, and measures include portal vein embolization and associating liver partition and portal vein ligation for staged hepatectomy. For HCC that has invaded a major vessel, en bloc resection with immediate vessel reconstruction is necessary if thrombectomy would not suffice. In case of bilobar involvement, radiofrequency ablation is a useful adjuctive therapy. In the treatment of extrahepatic metastasis, metastasectomy offers a cure to properly selected patients.

Aim: The short and long term outcomes of patients who underwent emergency and interval hepatectomy for ruptured and resectable hepatocellular carcinoma (HCC) were analysed.

Methods: The data of patients with ruptured HCC presenting between April 2004 and October 2015 were analysed. Emergency hepatectomy was defined as hepatectomy within 48 h of the clinico-radiological diagnosis of HCC rupture.

Results: Thirty patients underwent hepatectomy for ruptured HCC. Nine (30%) patients underwent emergency hepatectomy. The median age was 56 and 54 years (P = 0.13) with a similar gender distribution. The mean HCC size (10.5 vs. 8.3 cm, P = 0.17), total blood loss (3,000 vs. 850 mL, P = 0.002) and total units of red blood cell transfusion (1.9 vs. 0.5 units, P = 0.27) were greater in the emergency hepatectomy group. The complication rate was 44% and 38% (P = 0.53), with median length of hospital stay of 10 and 12 days (P = 0.07) in the emergency and interval hepatectomy groups, respectively, and no 30-day mortality in both groups. The median overall survival was 29 and 15.7 months (P = 0.25), with survival rates of 78%, 45%, 0% and 85%, 43% and 5% at 1, 3 and 5 years in the emergency and interval hepatectomy groups, respectively.

Conclusion: Hepatectomy should be considered for ruptured HCC provided the patient could tolerate curative resection.

The robotic surgical system was developed to overcome the disadvantages of conventional laparoscopic surgery. The use of robots in liver surgery was not well evaluated. This article aimed at reviewing robotic partial hepatectomy to conventional laparoscopic or open partial hepatectomy in terms of perioperative, oncologic, and healthcare costs for hepatocellular carcinoma (HCC). Studies were identified by searching MEDLINE and PubMed databases for articles from January 2004 to June 2017 using the keywords "laparoscopic hepatectomy", "robotic surgery", "robotic hepatectomy", and "hepatocellular carcinoma". Case reports were not included. The open conversion rate, overall morbidity rate, and mortality rate of robotic partial hepatectomy were reported as 0-14.3%, 0-27%, and 0-3%, respectively. Although little data regarding robotic approach for HCC have been reported, it appears to be better than open approach, particularly blood loss and hospital stay, and similar to conventional laparoscopic approach in terms of short term outcomes. The oncological outcomes were comparable to open or laparoscopic approach. Well-known advantages of the robotic system allow resection of tumor location over posterior and superior segments or major hepatectomy with more ease. The main disadvantage of robotic approach was its high cost. In conclusion, oncological data from homogenous series of HCC after robotic partial hepatectomy was needed. Robotic approach was safe to be an alternative option of minimally invasive hepatectomy for HCC. Its future implementation will depend on the advantages that it can provide over open or conventional laparoscopy approach.

Hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC) in places where chronic hepatitis B infection is endemic. Oral nucleos(t)ide analog (NA) therapy can reduce the risk of HCC, but cannot completely prevent its development. For HBV-related HCCs, viral inhibition by NAs can preserve or improve liver function, thereby increasing the chance of therapeutic intervention. After surgical resection, NAs can prevent reactivation of HBV, and also reduce the chance of de novo development of HCC in the remnant liver. For those who undergo liver transplantation, NAs are essential to prevent reactivation and graft hepatitis, but is not likely to prevent HCC recurrence, which is due to metastatic disease. The role of NAs for non-curable advanced HCC is less well defined. These include patients undergoing locoregional therapy, chemotherapy, or palliation. Although antiviral therapy can preserve liver function, which may be compromised by HBV, it is unable to prevent disease progression from HCC. At the time of HCC diagnosis, most patients will already be receiving NAs, and these patients should be maintained on therapy. For patients not on antiviral therapy at the time of HCC diagnosis, the decision to commence therapy is often determined by the stage of HCC and life expectancy. Patients undergoing curative therapy, or locoregional therapy/chemotherapy with reasonable life expectancy, should be commenced on antiviral therapy.