Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer-related deaths worldwide. Curative resection is frequently limited in Hong Kong by hepatitis B virus-related cirrhosis, and liver transplantation is the treatment of choice. Liver transplantation has been shown to produce superior oncological benefits, when compared to hepatectomy for HCC. New developments in the context of patient selection criteria, modification of organ allocation, bridging therapy, salvage liver transplantation and pharmaceutical breakthrough have improved the survival of HCC patients. In this article, we will share our experience in transplanting hepatitis B virus-related HCC patients in Hong Kong and discuss the recent progress in several areas of liver transplantation.

Since the beginning of the century, viral infection has become a widespread problem to public health globally. Recently, the latest newcomer of the Flaviviridae family, the Zika virus, has emerged as a potential global threat to human health. Due to lack of sufficient data at present, Zika infection has become a major cause of Zika fever, central nervous system malformations such as microcephaly, severe neuroimmunopathology, fetal abnormalities, and recently Guillain-Barre syndrome. The lack of genomic as well as proteomic information keeps the Zika virus under examination by a multitude of researchers. The rapid increase in Zika viral infections has been classified as a public health emergency by the World Health Organization. Neither preventive antiviral drugs nor effective vaccines are available on the market for combating Zika infection. Urgent innovative research is necessary to facilitate the development of protective and fruitful therapeutic agents, to improve lifespan of individuals throughout the world. Thus, we present this review to summarize the current research findings for Zika viral infection and to highlight the importance of computational drug discovery in the development of potent antiviral inhibitors against the Zika virus. We also anticipate that the information in this review will present a valuable opportunity for the prediction of efficient novel therapeutic remedies for controlling Zika.

Spontaneous or intended conversion of atrial fibrillation (AF) to sinus rhythm is associated with a short-term increase from baseline risk of clinical thromboembolism. Guidelines suggest performing cardioversion without prior execution of trans esophageal echo (TEE) if the patient has completed a month of anticoagulation with warfarin (in the therapeutic international normalized ratio range) or non-vitamin K antagonist oral anticoagulants (NOACs).

We performed TEE echo in 100 consecutive patients taking NOACs or warfarin for 1 month or more, to see if there was evidence of left arterial appendage thrombi or extremely low flow velocity (<40 cm/s) that can increase risk of ischemic events after cardioversion.

Even in patients with correct anticoagulation therapy, thrombi can be found in the left atrial appendage. For this reason, until further data are present, we suggest executing TEE before direct current cardioversion. Moreover, NOAC was shown to be safe for use before cardioversion. The only exception was with rivaroxaban, so we suggest further analysis with larger samples to determine the mechanisms underlying this finding.

Even if cardioversion can be performed without prior TEE after 1 month of anticoagulation therapy, we think that (except in patients with very low risk of thrombosis) it is preferable to execute this exam before trying to restore sinus rhythm.

Non-alcoholic fatty liver disease (NAFLD), the most common cause of liver disease, affects approximately 75 to 100 million Americans. Patients with concurrent NAFLD and type 2 diabetes mellitus have a higher risk of progressing to advanced fibrosis and non-alcoholic steatohepatitis compared to non-diabetics. Lifestyle modifications, including weight loss, remain the mainstay of treatment for NAFLD, as there are no medications currently indicated for this disease state. Anti-diabetic pharmacologic therapies aimed at improving insulin sensitivity and decreasing insulin production have been studied to determine their potential role in slowing the progression of NAFLD. In this review, we focus on the evidence surrounding anti-diabetic medications and their ability to improve disease progression in patients with NAFLD.

Tight junction and cell polarity proteins are paramount to epithelial cell polarity and transport. In vivo studies have shown the differential expression of tight junctions in colorectal cancer, with little to no human data to corroborate those findings. We investigated whether tight junction genes were differentially expressed in human colon cancer versus normal controls.

Total RNA was extracted from fresh frozen tumor tissues and normal adjacent tissues of 6 patients who were diagnosed with primary colon cancer as well as from normal mucosa of 5 unrelated polyp-free individuals. We used the Qiagen RT2 Profiler PCR array to determine the expression of 84 genes in the tight junction pathway. Student’s t-test was used to compare gene expression levels between cancer tissues and normal mucosa using normalized gene expression data.

Compared with normal mucosa, significant up-regulation of the claudin 1 (CLDN1) gene (fold-change = 16, p = 0.001) but down-regulation of the AMOTL1, CLDN5, JAM2 and TIAM1 genes (fold-change > 2, p < 0.05) were seen in colon cancer tissue.

We observed the differential expression of CLDN, AMOTL1, JAM2 and TIAM1 in colon cancer versus normal mucosa. Further larger studies are warranted to investigate the role of tight junction and cell polarity proteins in the progression of human colon tumors.

Background and Aims: Hepatitis B surface antigen (HBsAg) loss is seldom achieved with nucleos(t)ide analog (NA) therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon (Peg-IFN) alfa-2a. We assessed HBsAg loss with 48- and 96-week Peg-IFN alfa-2a in chronic hepatitis B patients with partial response to a previous NA.

Methods: Hepatitis B e antigen (HBeAg)-positive patients who achieved HBeAg loss and hepatitis B virus DNA <200 IU/mL with previous adefovir, lamivudine or entecavir treatment were randomized 1:1 to receive Peg-IFN alfa-2a for 48 (n = 153) or 96 weeks (n = 150). The primary endpoint of this study was HBsAg loss at end of treatment. The ClinicalTrials.gov identifier is NCT01464281.

Results: At the end of 48 and 96 weeks’ treatment, 14.4% (22/153) and 20.7% (31/150) of patients, respectively, who switched from NA to Peg-IFN alfa-2a cleared HBsAg. Rates were similar irrespective of prior NA or baseline HBeAg seroconversion. Among those who cleared HBsAg by the end of 48 and 96 weeks’ treatment, 77.8% (14/18) and 71.4% (20/28), respectively, sustained HBsAg loss for a further 48 weeks. Baseline HBsAg <1500 IU/mL and week 24 HBsAg <200 IU/mL were associated with the highest rates of HBsAg loss at the end of both 48- and 96-week treatment (51.4% and 58.7%, respectively). Importantly, extending treatment from 48 to 96 weeks enabled 48.3% (14/29) more patients to achieve HBsAg loss.

Conclusions: Patients on long-term NA who are unlikely to meet therapeutic goals can achieve high rates of HBsAg loss by switching to Peg-IFN alfa-2a. HBsAg loss rates may be improved for some patients by extending treatment from 48 to 96 weeks, although the differences in our study cohort were not statistically significant. Baseline and on-treatment HBsAg may predict HBsAg loss with Peg-IFN alfa-2a.

The role of metabolism (basal metabolic rate (BMR)) in asthma remains dubious. Seasonal variations are reported in both BMR and asthma, with the former increasing in winter and decreasing in summer. Correlation between metabolism and asthma treatment is not obvious in the literature; therefore, it was planned to assess role of substances which alter metabolism in managing asthma.

This was a randomized double-blind active control trial, in which 400 confirmed asthma cases were divided into two groups (group 1 (control) and group 2 (study)), with group 2 further subdivided into two (subgroups 2A and 2B). The study period was from January to December 2016. During attack, group 2A was given kitchen spices (cloves, bay leaf, black pepper; substance A) and 2B was given cool substances (rose petal jam; substance B). The control group was given inhaled levosalbutamol. Symptoms and peak expiratory flow rate (PEFR) were recorded. Improvement was suggested by reduction in symptoms and improvement in PEFR. Review of symptoms was done at 24 and 72 h and of PEFR at 72 h after the therapy. Statistical significance of differences between group 1 and 2A and 2B was calculated by the chi-square test by using SPSS 20 software.

Exacerbations were found in February (season: winter), March (spring), August (rainy) and October (autumn). In February and March, the response was significant with substance A (p < 0.001), but substance B had poor response. In August and October, the response was significant with substance B (p < 0.001), and substance A had insignificant response.

Substances which increase BMR are helpful in winters and high metabolic state of the body, and conversely. Change in metabolism possibly effects heat and water losing/preserving effect of the body, including related to the respiratory tract (thermoregulation), and lessens inflammation in the respiratory tract.

Background and Aims: DNA methylation and histone modification are epigenetic modifications essential for normal function of mammalian cells. The processes are mediated by biochemical interactions between DNA methyltransferases (DNMTs) and histone deacetylases. Promoter hypermethylation and deacetylation of tumor suppressor genes play major roles in cancer induction, through transcriptional silencing of these genes. DNA hypermethylation is carried out by a family of DNMTs including DNMT1, DNMT3a and DNMT3b. In hepatocellular carcinoma, a significant positive correlation between over-expression of these genes and cancer induction has been reported. The DNA demethylating agent genistein (GE) has been demonstrated to reduce different cancers. Previously, we reported that GE can induce apoptosis and inhibit proliferation in hepatocellular carcinoma PLC/PRF5 and HepG2 cell lines. Besides, histone deacetylase inhibitors, such as trichostatin A (TSA), were successfully used to inhibit cancer cell growth. The present study was designed to assess the effect of GE in comparison with TSA on DNMT1, DNMT3a and DNMT3b gene expression, cell growth inhibition and apoptosis induction in the HepG2 cell line.

Methods: Cells were seeded and treated with various doses of GE and TSA. The MTT assay, flow cytometry assay, and real-time RT-PCR were used to determine viability, apoptosis, and DNMT1, DNMT3a and DNMT3b gene expression respectively.

Results: Both agents inhibited cell growth, induced apoptosis and reactivated DNMT1, DNMT3a and DNMT3b gene expression. Furthermore, TSA demonstrated a significantly greater apoptotic effect than the other agent, whereas GE improved gene expression more significantly than TSA.

Conclusions: Our findings suggest that GE and TSA can significantly inhibit cell growth, induce apoptosis and restore DNMT1, DNMT3a and DNMT3b gene reactivation.

Many clinical conditions exist in which it is desirable to stimulate or suppress the immune system, and many different drugs are able to do this. It is also well known that nutrition may affect human health and immune responses. Nutritional factors are crucial components of the diet, essential for the normal growth and development of both vertebrate and invertebrate organisms. Many of these components have been shown to play different roles in the immune response, and under different circumstances they can significantly modulate the immune system to create an effective response. The aim of the present review was to show the effect of a biomarine lipofishin (E-JUR-94013) obtained from the species T. trachurus, present on the Galician coast of the Atlantic Ocean, in the improvement of immune system function. In humans, the results obtained under different clinical conditions clearly demonstrated the ability of E-JUR-94013 to improve the host innate and acquired immune responses. In three different clinical studies, 56, 205 and 1,500 patients were included, respectively. All patients were supplemented with 750 mg/day of E-JUR-94013. In the first study, significant increases in IgA (p = 0.033) and IgG, and a reduction in IgE (p = 0.033) were observed. In the second study, a normalization in leukocyte cell counts after treatment was observed (p < 0.05). The main objective of the last study was to correlate inflammatory genotypes with response to E-JUR-94013. The results obtained indicated that high ultrasensitive C-reactive protein was down-regulated. In addition, both IL-6-C573G and IL1β-T3954C genotypes clearly correlated with response to E-JUR-94013 treatment. Taken together, these results suggest that supplementation of diets with E-JUR-94013 can be employed to improve, enhance and regulate certain immune responses and lead to increased resistance to disease.

Chronic stress plays a central role in the pathogenesis of psychiatric disorders. A sensory contact model induces mixed anxiety/depression-like behaviors. Repeated experience of victories or defeats may change neurophysiological status, the immune system and brain neurochemistry in opposite directions. The objective of this study was, therefore, to establish a sensory contact model for studying the impact of psychosocial stress in mice and investigate its influence on behavioral, neurochemical and immunological changes of both winners and losers.

Four groups of male mice were used, including two groups that received saline and either in normal housing or caged individually for 5 days; the others were subjected to sensory contact modeling for 21 days. All mice were subjected to open-field test, after which blood samples were collected for evaluation of total and differential leukocyte count and brain homogenate was used to estimate monoamines.

Social isolation reduces serotonin and neutrophils while elevating most other parameters. Winners also showed reduction in serotonin and neutrophils, as compared to controls which showed reduction in grooming time, total leukocyte count, neutrophils associated with elevation in monocytes and eosinophils as compared to isolation group. On the other hand, losers showed elevation in grooming time, dopamine, norepinephrine, lymphocytes, monocytes, eosinophils associated with reduction in ambulation, serotonin and neutrophils as compared to all groups. They also showed reduction in rearing and elevation in total leukocyte count as compared to winners.

Social stress leads to severe depression and anxiety-related behaviors; losers were more depressed than winners. However, aggressive behavior was increased in winners, while locomotor and exploratory activities were decreased, indicating decreased anxiety and emotional distress. The immune function was enhanced to higher extent in losers than winners, which can be attributed to sensation of threat and trauma in losers.

Alzheimer’s disease (AD) is a major health problem in developed countries. The absence of specific biomarkers for diagnosis and the multiple limitations of available screening methods have slowed down the efficient implementation of AD population-based screening programs. Based on recent developments, we have designed and tested a new AD vaccine tool kit as an effective framework for large-scale animal model screening. The AD vaccine tool kit was developed for transgenic animal models of AD in order to evaluate their neuropathological characteristics via multiple screening strategies.

This vaccine consists of the inoculation of a new immunogen-adjuvant designed to specifically activate antibodies against the generation of neuritic plaques produced by the toxic excess of amyloid-β (Aß) and simultaneously to deal with the autoimmune activation that triggers acute meningoencephalitis, as observed in human trials in the past.

In the present study, we show the current status of the AD vaccine tool kit, with a special focus on the evaluated data and its available settings. We also review the strengths and limitations of this kit in the context of its applicability in experimental research.

We focus our attention on the ‘framework experimental immunization guidelines’ for AD screening, which have recently been boosted by numerous research lines implemented throughout the scientific community.

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and the second leading cause of cancer-related deceases worldwide. Early diagnosis is essential for correct management and improvement of prognosis. Proposed for the first time in 2011 and updated for the last time in 2017, the Liver Imaging-Reporting and Data System (LI-RADS) is a comprehensive system for standardized interpretation and reporting of computed tomography (CT) and magnetic resonance imaging (MRI) liver examinations, endorsed by the American College of Radiology to achieve congruence with HCC diagnostic criteria in at-risk populations. Understanding its algorithm is fundamental to correctly apply LI-RADS in clinical practice. In this pictorial review, we provide a guide for beginners, explaining LI-RADS indications, describing major and ancillary features and eventually elucidating the diagnostic algorithm with the use of some clinical examples.

Imaging plays a crucial role in the diagnosis of hepatocellular carcinoma (HCC) as well as in determining treatment efficacy, or complications, following therapy. Unlike other cancers, HCC is most commonly treated by locoregional therapies (LRTs) such as thermal ablation, transarterial chemoembolization, and transarterial radioembolization. These treatments can lead to changes on imaging that make determination of residual/recurrent disease difficult. This literature-based review discusses the expected postimaging findings following LRT.