Autoimmune hepatitis has been considered as a relatively rare immunological liver disease, especially in the Asia-Pacific area. Although the diagnosis criteria and immunosuppressive treatment regimens have been established, there are still some challenges. According to the different presentations, the personalized management of patients who suffer from this disease, including those with chronic or acute severe onset, the autoantibody-negative phenotype and cirrhosis are necessarily descriptive. Each subgroup of patients should receive an individualized therapy. Here, we review the recent studies of autoimmune hepatitis, mainly focusing on the epidemiology and genetics, personalized diagnostics, individualized treatment strategies, special subgroups and outcomes. Most of the research in the literature is based on Japanese and Chinese populations.

Chylous ascites (CA) is a rare form of ascites that results from the leakage of lipid-rich lymph into the peritoneal cavity. This usually occurs due to trauma and rupture of the lymphatics or increased peritoneal lymphatic pressure secondary to obstruction. The underlying etiologies for CA have been classified as traumatic, congenital, infectious, neoplastic, postoperative, cirrhotic or cardiogenic. Since malignancy and cirrhosis account for about two-thirds of all the cases of CA in Western countries, in this article we have attempted to reclassify CA based on portal and non-portal etiologies. The diagnosis of CA is based on the distinct characteristic of the ascitic fluid which includes a milky appearance and a triglyceride level of >200 mg/dL. The management consists of identifying and treating the underlying disease process, dietary modification, and diuretics. Some studies have also supported the use of agents such as orlistat, somatostatin, octreotide and etilefrine. Paracentesis and surgical interventions in the form of transjugular intrahepatic portosystemic shunt (commonly known as TIPS), peritoneal shunt, angiography with embolization of a leaking vessel, and laparotomy remain as treatment options for cases refractory to medical management.

Melaleuca viminalis (syn. Callistemon viminalis, red bottle brush) and Melaleuca armillaris (white Bottle brush) belong to the family Myrtaceae and are reported for their traditional medicinal properties. The objective of this study was to explore and compare the chemical compositions and biological properties of these two species.

Sequential extraction and hydro-distillation methods were employed to extract essential oils for further analysis of chemical composition by gas chromatography-mass spectrometry (GC-MS). The biological potential as antioxidants was investigated for both species by assessing 1,1-diphenyl-2-picrylhydrazyl (commonly known as DPPH) scavenging activity and by use of ferric iron reducing assay. The biological potential as antibacterials was investigated by agar well diffusion assay. The in vitro cytotoxicity analysis was carried out by MTT assay.

GC-MS analysis of the essential oil of Melaleuca viminalis indicated the presence of eucalyptol as the principal chemical constituent, while that of Melaleuca armillaris indicated the presence of methyl eugenol. Comparative studies indicated that Melaleuca viminalis had higher potential for antioxidant and antibacterial activities than Melaleuca armillaris. Also, the essential oil of Melaleuca viminalis exhibited in vitro cytotoxicity against the cancer cell lines of A549 (lung; IC50 24.12 µg/mL), HCT-116 (colon; IC50 21.5 µg/mL) and T47D (breast; IC50 21.78 µg/mL), in comparison to Melaleuca armillaris for which cytotoxicity was only observed against theA549 (IC50 10.2 µg/mL) lung cancer cell line.

The present findings suggest that essential oil of Melaleuca viminalis (leaves) hold potential for future application in various medical procedures. However, the presence of methyl eugenol in Melaleuca armillaris raises concern of its being acarcinogenic compound, so further detailed toxicological studies are required to validate its therapeutic potential.

Liver resection is increasingly used for a variety of benign and malignant conditions. Despite advances in preoperative selection, surgical technique and perioperative management, posthepatectomy liver failure (PHLF) is still a leading cause of morbidity and mortality following liver resection. Given the devastating physiological consequences of PHLF and the lack of effective treatment options, identifying risk factors and preventative strategies for PHLF is paramount. In the past, a major limitation to conducting high quality research on risk factors and prevention strategies for PHLF has been the absence of a standardized definition. In this article, we describe relevant definitions for PHLF, discuss risk factors and prediction models, and review advances in liver assessment tools and PHLF prevention strategies.

The ability of plants to exert health benefits beyond antioxidant and micronutrient capacity introduces a gap in scientific understanding. The xenohormesis hypothesis aims to fill this gap, proposing that an evolutionary adaptation of enzyme and receptor pathways allow us to react to information that plants provide about the environment, offering a distinct survival advantage. The concept suggests that phytochemicals produced by plants under stress are able to activate longevity pathways in other organisms when consumed. The same pathways activated by calorie restriction, the highly conserved sirtuin enzymes and cellular homeostasis mechanisms provide an exciting perspective for treating chronic conditions related to excessive consumption. Harnessing the biological activity associated with the xenohormesis paradigm could provide a simple and achievable therapeutic alternative, although it needs to be considered within the confounding framework. The objective of this paper is to provide an update on the role of xenohormesis within nutritional medicine and to discuss the impact of modern food supply and consumption practices on evolutionary processes.

To synthesize 2-naphthylamine analogs containing azetidin-2-one (4a–g) and thiazolidin-4-one (5a–g) ring moiety, with the aim of finding new potent antimicrobial agents.

The antimicrobial activities (antibacterial and antifungal) of the newly-prepared compounds were tested in vitro against bacterial cultures (Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa) and fungal culture (Candida albicans) using agar plate diffusion antimicrobial bioassay. The structures of the title compounds were supported by their spectral data (IR, 1H NMR and 13C NMR).

The synthetic methodology used for the synthesis of the title compounds is shown in Scheme 1 in the paper. Among all the prepared analogs, four compounds (4a, 4e, 4g and 4f) exhibited broad spectrum activity, as compared to the standard drug (ampicillin). Another three compounds (3b, 5b and 5e) showed remarkable antifungal activity, as compared with the standard drug (amphotericin B).

The present investigation led to the synthesis and biological evaluation of naphthylamine analogs having azetidin-2-one and thiazolidin-4-one heterocyclic nucleus/moiety.

Vitamin D has been linked to brain function. To date, there have been limited studies investigating vitamin D receptor (VDR) genetic polymorphisms and cognition. The objective of this study was, therefore, to examine whether any relationships exist between VDR polymorphisms and cognitive decline in an elderly population.

Six hundred and fifty participants aged ≥ 65 years were recruited from the Central Coast, New South Wales, Australia, and were genotyped for 8 VDR polymorphisms (VDR-ApaI, VDR-BsmI, VDR-TaqI, VDR-FokI, VDR-Tru91, VDR-Cdx2, VDR-A1012G, and VDR-NIaIII). Gene variants were identified using polymerase chain reaction, followed by restriction fragment length polymorphism analysis and gel electrophoresis. Cognitive decline was measured using the mini-mental state examination (MMSE), while a self-administered food frequency questionnaire was used to estimate participants’ dietary intake of vitamin D.

Odds ratio (OR) analysis found that VDR-BsmI and VDR-TaqI polymorphic alleles were both associated with increased risk of cognitive decline (OR = 1.55 and OR = 1.49, respectively). VDR-TaqI was also found to be significantly associated with MMSE score, following adjustment for age and sex (p = 0.0005). Examination of the distribution of VDR-TaqI genotypes showed that a greater proportion of participants with the homozygous recessive tt genotype had some degree of cognitive decline (24%). As might be predicted, a significant association was also observed between age and MMSE score (p = 0.015). When examined by sex, a significant relationship was found between age and MMSE for females (p ≤ 0.0001) but no relationship was observed in males. Dietary intake of vitamin D did not influence MMSE outcomes in this cohort.

The VDR-BsmI and VDR-TaqI genetic polymorphisms are associated with cognitive decline in an elderly population.

Cases of suspected herb-induced liver injury (HILI) caused by herbal Traditional Chinese Medicines (TCMs) and of drug-induced liver injury (DILI) are commonly published in the scientific literature worldwide. As opposed to the multiplicity of botanical chemicals in herbal TCM products, which are often mixtures of several herbs, conventional Western drugs contain only a single synthetic chemical. It is therefore of interest to study how HILI by TCM and DILI compare with each other, and to what extent results from each liver injury type can be transferred to the other. China is among the few countries with a large population using synthetic Western drugs as well as herbal TCM. Therefore, China is well suited to studies of liver injury comparing drugs with TCM herbs. Despite some concordance, recent analyses of liver injury cases with verified causality, using the Roussel Uclaf Causality Assessment Method, revealed major differences in HILI caused by TCMs as compared to DILI with respect to the following features: HILI cases are less frequently observed as compared to DILI, have a smaller proportion of females and less unintentional rechallenge events, and present a higher rate of hepatocellular injury features. Since many results were obtained among Chinese residents who had access to and had used Western drugs and TCM herbs, such ethnic homogeneity supports the contention that the observed differences of HILI and DILI in the assessed population are well founded.

Locoregional therapy is playing an increasingly important role in the non-surgical management of hepatocellular carcinoma (HCC). The novel technique of non-thermal electric ablation by nanosecond pulsed electric field has been recognized as a potential locoregional methodology for indicated HCC. This manuscript explores the most recent studies to indicate its unique anti-tumor immune response. The possible immune mechanism, termed as nano-pulse stimulation, was also analyzed.

Background and Aims: Acute calculous cholecystitis with impending gall bladder perforation in severe liver diseases including decompensated cirrhosis and acute-on-chronic liver failure (ACLF) is difficult to manage, due to the procedures such as cholecystectomy and per cutaneous cholecystostomy being associated with high risk and complications in these patients.

Methods: Four cases of severe liver disease with acute calculous cholecystitis who presented to the Institute of Liver and Biliary Sciences (New Delhi, India) for further management were included in the study if they underwent endoscopic ultrasound-guided gall bladder drainage (EUS-GBD). The patients were followed up for a minimum of 3 months and outcomes were recorded.

Results: Four cases of severe liver disease (three ACLF and one decompensated cirrhosis), with model for end-stage liver disease scores of 24, 26, 23 and 25 respectively, presented with acute calculous cholecystitis (Tokyo grade III) and systemic sepsis (high total leukocyte counts). Their international normalized ratios were 2.3, 2.6, 2.2 and 2.9 respectively, and two were in shock, requiring inotropes at presentation. Ultrasonography of the abdomen confirmed hugely distended gall bladder with stone impacted at the neck and moderate ascites. All these cases underwent EUS-GBD by linear echo endoscope, and had the gastric wall punctured in the antrum using a 19G access needle followed by dilatation of the tract using controlled radial expansion balloon and Sohendra dilator. In three cases, the plastic stents were placed. In the fourth case, a Nagi stent was placed. All the patients recovered and were discharged within a week.

Conclusions: EUS-GBD is challenging in severe liver disease but represents a life-saving procedure, and hence can be attempted in such critically ill patients with utmost care and precaution.

Background and Aims: Few previous studies have reported on a combination response (hepatitis B virus (HBV) DNA undetected, alanine aminotransferase normalization and hepatitis B e antigen (HBeAg) seroconversion) following nucleos(t)ide analogue (NAs) long-term therapy in patients with chronic hepatitis B (CHB). This study aimed to investigate the combination response on long-term NAs therapy in patients with HBeAg-positive CHB and to determine whether prolonged therapy is beneficial for combination response, particularly in optimal patients (baseline alanine aminotransferase level ≥5 upper limit of normal and HBV DNA level <109 copies/mL).

Methods: In total, 280 HBeAg-positive CHB patients were enrolled in this study. Among them, 190 were treated with entecavir and 90 were treated with telbivudine.

Results: The cumulative rates of combination response in the total number of patients were 8.6% at 1 year, 13.2% at 2 years, 19.1% at 3 years, 24.2% at 4 years and 26.0% at 5 years. In optimal patients, the cumulative rate of combination response was significantly higher than that in the non-optimal patients at 3 years (p = 0.043); the trend of the cumulative rate was not strong at the later time. Interestingly, in optimal patients, combination response mainly occurred in the first 3 years. Multivariate analysis identified HBeAg/anti-HBe seroconversion at 1 year as the only factor for combination response in optimal patients (hazard ratio: 16.321; p = 0.000). During the 3 years, the proportion with aspartate aminotransaminase to platelet ratio index ≤0.5 increased from 15.6% at baseline to 71.3% at year 3.

Conclusions: Upgrading the rate of combination response is limited by prolonging the treatment duration of NAs from 3 years to 5 years in HBeAg-positive CHB patients; a new switch treatment strategy modification should be considered, particularly in optimal patients.

Collagenopathies are heterogeneous diseases that affect collagen proteins, which are ubiquitous in the body and characterized by the distinctive amino acid sequence Gly-X-Y. Next-generation sequencing (NGS) has gained an increasingly essential role in improving our understanding of the molecular bases of heterogeneous diseases like collagenopathies. In the last decades new NGS tools have been developed, such as whole exome sequencing (WES) and custom target sequencing, and they have become efficient and cost-effective methods for clinical diagnosis. In this review, we discuss the relevance of WES and custom target sequencing in the clinical diagnosis of collagenopathies.