Background and Aims: Skeletal manifestation in liver diseases represents the minimally scrutinized part of the disease spectrum. Vitamin D deficiency has a central role in developing hepatic osteodystrophy in patients with chronic liver disease. This study aimed to investigate vitamin D levels and their relationship with disease advancement in these patients.

Methods: Vitamin D levels were checked in 125 chronic liver disease patients. The patients were classified in three stages according to Child-Pugh score: A, B and C. The relationship of vitamin D levels with Child-Pugh score and other variables in the study was assessed by the contingency coefficient. Correlation and logistic regression analyses were also carried out to find additional predictors of low vitamin D levels.

Results: Among the patients, 88% had either insufficient or deficient stores of vitamin D, while only 12% had sufficient vitamin D levels (p >0.05). Vitamin D levels were notably related to Child-Pugh class (contingency coefficient = 0.5, p <0.05). On univariate and multinomial regression analyses, age, female sex, MELD and Child-Pugh class were predictors of low vitamin D levels. Age, model of end-stage liver disease score and Child-Pugh score were negatively correlated to vitamin D levels (p <0.05).

Conclusions: Vitamin D deficiency is notably related to age, female sex and model of end-stage liver disease score, in addition to Child-Pugh class of liver cirrhosis. Vitamin D levels should be routinely checked in patients with advanced liver cirrhosis (Child-Pugh class B and C) and this deficiency must be addressed in a timely manner to improve general well-being of cirrhotic patients.

Dietary fat type can differentially modulate the fatty acid oxidation and secretion of lipoproteins in hepatocytes. The purpose of the present study was to investigate how the nature of fatty acids present in dietary oils influences fatty acid oxidation as well as secretion of apolipoproteins.

Primary rat hepatocytes were cultured with major fatty acids present in common cooking oils, which vary in their degree of saturation: viz. coconut oil (lauric acid; C12:0); olive oil (oleic acid; C18:1); and sunflower oil (linoleic acid; C18:2). Each fatty acid was used at a dose of 500 µM for 12 hours.

Cells treated with laurate beneficially modulated the secretion of apolipoproteins relative to cells treated with oleate and linoleate (p < 0.05). These results correlated with the respective apolipoproteins’ mRNA expression. Laurate increased activities and mRNA expression of enzymes involved in β-oxidation (viz. carnitine palmitoyl transferase I and acyl CoA oxidase) and also up-regulated the respective transcription factor, peroxisome proliferator-activated receptor alpha (PPARα), when compared to other fatty acids (p <0.05). Studies using the PPARα agonist WY 14643 revealed that lauric acid may act as a natural ligand for PPARα and mediates its effects partly via PPARα-dependent pathways in hepatocytes.

These results clearly indicate that lauric acid, the major fatty acid present in oil extracted from coconut, acts as a natural ligand for PPARα, beneficially regulating secretion of apolipoproteins and enhancing fatty acid oxidation via PPARα signaling pathways in hepatocytes.

Whereas statistical association of hepatitis C virus (HCV) infection with cardiomyopathy is long known, establishment of a causal relationship has not been achieved so far. Patients with advanced heart failure (HF) are mostly unable to tolerate interferon (IFN)-based treatment, resulting in limited experience regarding the possible pathogenic role of HCV in this patient group. HCV infection often triggers disease in a broad spectrum of extrahepatic organs, with innate immune and autoimmune pathogenic processes involved. The fact that worldwide more than 70 million patients are chronically infected with HCV illustrates the possible clinical impact arising if cardiomyopathies were induced or aggravated by HCV, resulting in progressive HF or severe arrhythmias. A novel path has been opened to finally resolve the long-standing question of cause-effect relationship between HCV infection and cardiac dysfunction, by the recent development of IFN-free, highly efficient, and well tolerable anti-HCV regimens. The new direct-acting antiviral (DAA) agents are highly virus-specific and lack unspecific side-effects upon cardiac function which have always confounded the interpretation of IFN treatment data. The actual frequency of unexplained HF in chronic HCV infection will be determined from a planned large-scale study. Whereas such patients probably constitute a rather small fraction of all those harboring HCV, they have major clinical relevance. It is not yet known which fraction of these patients will significantly benefit from HCV eradication, but this issue will be addressed now in a prospective study.

Hepatitis E virus infection is usually a self-limited disease. However, during the last years there has been growing evidence for prolonged and chronic infection occurring in patients with immunosuppression. Also patients with malignant and rheumatic diseases have been identified to be at risk for chronic hepatitis E. However, their course and prognosis are not well characterized and there have been no reports of hepatitis E virus infection in patients with gynecological cancer. Here, we report three Caucasian females with breast and ovarian cancers presenting with elevation of aminotransferase levels during anticancer treatment. Although only few or no clinical hints suggested hepatitis E virus infection, the diagnosis of hepatitis E virus infection was confirmed by seroconversion, which might occur with some delay, and/or by polymerase chain reaction. While two patients had a self-limited course, the third patient with a high-risk oncological constellation required ribavirin in order to resume chemotherapy. These cases highlight the need for hepatitis E virus testing in patients with gynecological cancer and elevated aminotransferase levels. Further, these cases show that in selected high-risk patients, ribavirin treatment may be necessary based on the decision of a multidisciplinary team.

Background and Aims: The use of additional nucleos(t)ide analogues (NAs) without cross-resistance to previously used NAs as a rescue therapy is recommended by most international guidelines for chronic hepatitis B patients with NA-resistance. We aimed to investigate the efficacy and safety of combination therapy of peg-interferon (PegIFN) alfa-2a and NA in these patients, comparing to those who switch to an alternative NA therapy without cross-resistance.

Methods: In this prospective, comparative and cohort study, data were collected from the patients’ hospital records. Eligible patients were those with hepatitis B e antigen (HBeAg) positivity and resistance to one or more NAs. All patients were treated with alternative NA alone or in combination with PegIFN alfa-2a for 52 weeks or 72 weeks, respectively. HBeAg seroconversion was measured at the end of follow-up (EOF; more than 104 weeks after the end of treatment).

Results: Sixty-three patients were recruited to the cohort study (NA-therapy group = 31 patients; combination therapy group of NA and PegIFN alfa-2a = 32 patients). At the EOF, significantly more patients in the combination therapy group (13/27, 48.2%) achieved primary outcome of HBeAg seroconversion than those in the NA therapy group (4/32, 12.5%) (p = 0.003). Four patients (14.8%) in the combination therapy group achieved hepatitis B surface antigen (HBsAg) loss and HBsAg seroconversion, but none in the NA therapy group did (p = 0.039). In the combination therapy group, 16 patients (51.6%) achieved HBeAg seroconversion at the end of treatment, of which, 11 patients (68.8%) maintained the response until EOF.

Conclusions: Adding on PegIFN alfa-2a in combination with NA therapy might be an appropriate rescue treatment option for patients who have prior NA resistance. In addition, combination therapy induced sustained off-treatment biochemical responses in these patients.

Liver fibrosis (LF), a common consequence of chronic liver diseases with various etiologies, is characterized by excessive accumulation of macromolecules, including collagen, glycoproteins and proteoglycans, in the liver. LF can result in hepatic dysfunction, cirrhosis, portal hypertension and, in some cases, hepatocellular carcinoma. As the current gold standard for diagnosing LF, liver biopsy, however, is invasive and prone to sampling errors and procedure-related complications. Therefore, developing noninvasive, precise and reproducible imaging tests for diagnosing and staging LF is of great significance. Conventional ultrasound (US), computed tomography (CT) and magnetic resonance (MR) imaging can depict morphological alterations of advanced LF, but have relatively limited capability characterizing early-stage LF. In order to optimize the diagnostic performances of noninvasive imaging techniques for LF across its entire spectrum of severity, a number of novel methods, including US elastography, CT perfusion imaging and various MR imaging–based techniques, have been established and introduced to clinical practice. In this review, we intended to summarize current noninvasive imaging techniques for LF, with special emphasis on the possible roles, advantages and limitations of the new emerging imaging modalities.

Hepatic cysts (HCs) are frequently discovered incidentally on abdominal imaging. The prevalence of HCs has been reported as high as 15–18% in the United States. Although most cysts are benign, some are malignant or premalignant. It is important to diagnose cystic lesions in order to properly manage them. Imaging with conventional ultrasound, computed tomography, magnetic resonance imaging, or contrast-enhanced ultrasound can be used to further characterize and diagnose HCs. Ultrasound is typically the first-line imaging modality, whereas more advanced imaging can help narrow down the specific lesion. Contrast-enhanced ultrasound is a newer modality, recently approved in the United States, which offers non-invasive evaluation in real-time. The first step in diagnosis is stratifying risk by differentiating simple and complex cysts. There are several features that can help identify HCs, including septae, mural consistency, calcifications, and quality of cystic fluid. Simple cysts are mainly congenital cysts, but also occur in polycystic liver disease. Complex cysts include mucinous neoplasms, echinococcal cysts, hemorrhagic cysts, cystic hepatocellular carcinoma and other rare lesions. Treatment is indicated in symptomatic cysts or those suspicious for malignant or premalignant features. Treatment modalities include fenestration, aspiration sclerotherapy, or surgical resection.

Hepatocellular carcinoma (HCC) is a common cause of cancer-related death, with incidence increasing worldwide. Unfortunately, the overall prognosis for patients with HCC is poor and many patients present with advanced stages of disease that preclude curative therapies. Diagnostic and interventional radiologists play a key role in the management of patients with HCC. Diagnostic radiologists can use contrast-enhanced computed tomography (CT), magnetic resonance imaging, and ultrasound to diagnose and stage HCC, without the need for pathologic confirmation, by following established criteria. Once staged, the interventional radiologist can treat the appropriate patients with percutaneous ablation, transarterial chemoembolization, or radioembolization. Follow-up imaging after these liver-directed therapies for HCC can be characterized according to various radiologic response criteria; although, enhancement-based criteria, such as European Association for the Study of the Liver and modified Response Evaluation Criteria in Solid Tumors, are more reflective of treatment effect in HCC. Newer imaging technologies like volumetric analysis, dual-energy CT, cone beam CT and perfusion CT may provide additional benefits for patients with HCC.

Crohn’s disease in childhood accounts for about 25% of the overall prevalence of this condition, and compared with adult-onset disease has unique characteristics in being more likely to involve the colon, being more aggressive in behavior, and requiring early escalation of therapy. Exclusive enteral nutrition has proven to be an effective therapy, especially in children. There are various hypotheses regarding mode of action; however, the precise mechanisms are yet to be established. The aim of this paper is to provide an up-to-date review of the efficacy and mechanism of action of exclusive enteral nutrition in Crohn’s disease. A PubMed search was performed using the terms ‘mechanism of action’, ‘exclusive enteral nutrition’, ’partial enteral nutrition’, ‘nutritional therapy’, ‘children’, ‘paediatric’, ‘Crohn’s disease’. Relevant articles were selected from this search. In addition, the reference lists of these papers were scrutinized for further relevant publications. There is significant evidence for efficacy of exclusive enteral nutrition and some evidence for a number of mechanisms, including alteration of the gut microbiome, a direct anti-inflammatory effect at the mucosal level, and through alteration in the fat content within the diet. Exclusive enteral nutrition provides benefits beyond disease remission, especially through promoting growth; further studies are required to elucidate exactly how it works and the longer-term outcomes. This is particularly important given the lack of negative effects compared with the significant side-effect profile of biological therapies. Improving resources to minimize the psycho-social impact of exclusive enteral nutrition may open the way for wider use in adult patients through the development of solid diet alternatives to liquid feeds.

Diet is an important modifiable determinant of disease, and it is becoming clear that diet and genetic risk factors are interactive in determining risk for diseases such as cardiovascular disease, diabetes and cancers. Advances in technology have improved our understanding of gene-nutrient interactions, and lead to the development of nutrigenetics, personalized nutrition based on genetics. While evidence is strong for some associations, others remain unclear. As such, the implementation of nutrigenetics remains controversial. While some argue it is not ready for clinical use, it has also been argued that nutrigenetics is unfairly held to a higher standard than traditional nutrition research. Despite the future promise of nutrigenetic testing for improving health outcomes, several barriers in science, technology, acceptance and ethics exist to its implementation. Gene-nutrient associations have been identified in a number of lifestyle-associated diseases, and better understanding of these relationships may lead to improved health outcomes. However, the success of nutrigenetics is not only dependent on the strength of the science, but in consumer acceptance and uptake. This narrative review provides an overview of the current landscape for nutrigenetics in relation to key disease states, and addresses the potential barriers to implementation.

Type 2 diabetes is one of the most common chronic disease conditions, accounting for the majority of the 415 million diabetes cases worldwide. Australia currently has 1.7 million diabetics, with a prevalence among Australian Aboriginal and Torres Strait Islander populations 4–5 times that seen in non-indigenous Australians. The financial burden amounts to AU$14.6 billion per year. Known risk factors for type 2 diabetes are being overweight or obese, hypertension, a sedentary lifestyle, low concentration of high density lipoprotein, depression and family history. Nutrient restriction during pregnancy can program alterations to organs and systems in the developing fetus due to intrauterine growth restriction. This plasticity, known as the ‘thrifty phenotype’, has been implicated in a wide range of adult disease conditions, including type 2 diabetes. Developmental programming via epigenetic mechanisms has resulted in a reduction of pancreatic beta cell mass, disruption of glucose transport proteins and signaling, and earlier onset of glucose intolerance of offspring, and is transgenerational in nature. Indigenous populations around the world appear to be at greater risk of programming effects, thought to be a consequence of rapid dietary and lifestyle changes. Interventions aimed at ensuring adequate maternal nutrition may reduce the extent of the deleterious epigenetic modifications and reduce the prevalence of type 2 diabetes in Australian Aboriginal and Torres Strait Islander populations.

Folate has been proposed to be an efficacious treatment strategy for depression. The mandatory fortification of flour with synthetic folic acid (FA) in over 80 countries has yielded improvements in folate intake; however, depression is still a considerable public health concern. While there are established benefits of FA fortification in reducing risk of neural tube defects, the implications regarding depression are unclear, especially in individuals with certain genetic polymorphisms. Therefore, a systematic review was conducted to examine the effects of folate to treat depression. Following PRISMA guidelines, a systematic review was conducted of electronic databases (PUBMED, Scopus, CINAHL, and Cochrane Library) to identify human clinical trials examining the effects of folate (including FA) supplementation in the management or prevention of depression, the impact on inflammatory markers and if genetic polymorphisms were considered. Ten trials met the inclusion criteria. Seven trials examined effects of either adjunctive FA or L-methylfolate (L-MTHF) supplementation with antidepressants in the management of depression and three examined effects of FA supplementation alone for prevention of depression. No benefit of FA was found compared to placebo (all, p > 0.05). The single L-MTHF trial that explored the interplay of genetic polymorphisms and methylation status found benefit in the Hamilton depression rating scale from adjunctive treatment with 15 mg/day of L-MTHF compared with placebo (−6.8 ± 7.2 vs. −3.7 ± 6.5; p = 0.017) and improvement with L-MTHF for most genetic markers. Currently, there is no evidence to support FA supplementation for the management or prevention of depression. More research is required to determine the efficacy of L-MTHF and folinic acid in certain clinical populations.

The incidence of pancreatic cancer (PC) closely matches mortality, with current therapies ineffective often due to late diagnosis and difficulties in drug delivery. Bitter melon (Momordica charantia, Cucurbitaceae) has been traditionally used as an herbal medicine, particularly for the treatment of diabetes, in South East Asian countries. The aim of this study was to investigate the anti-PC potential of a crude ethanol extract (CE) and its enriched fractions.

The CE was used to prepare the saponin-enriched extract (SE) using n-butanol: water extraction. CE was also used for preparation of fractions 1, 2 and 3 (F1, F2 & F3) with a semi-preparative high-pressure liquid chromatography system. Cucurbitacin B (CuB), a triterpenoid present in many Cucurbitaceae species was also investigated for its effect on PC cells. The cytotoxicity was assessed in the PC cells MiaPaCa2, BxPC3 and CFPAC-1, and normal pancreas cells (HPDE) using the Cell Counting Kit-8 viability assay. Cell cycle analysis and induction of apoptosis in cells treated with F3 or CuB was determined using the Muse™ flow cell analyzer.

The CE reduced the viability of MiaPaCa2 cells without affecting the normal cells, but only at 1,000 µg/mL. The SE reduced viability of all cells; however, the GI50 was significantly lower for the HPDE cells (72h: 72.1 µg/mL HPDE vs. 350.8 µg/mL MiaPaCa2). F3 and CuB appeared to arrest the cell cycle at G1/0 and G2/M, respectively; however, only CuB induced apoptosis via increased expression of caspase 3/7.

The CE, SE and three fractions elicited a weak cytotoxic effect on PC cells. Further research into bitter melon is recommended to isolate and identify any active components in F3 and further investigate their potential as novel agents against PC.

Recognition and diagnosis of sports-related concussion (SRC) among adolescents has significantly increased. In, fact, among high school adolescents, SRC incidence has more than doubled from 2007 to 2014, with recent estimates at approximately 2 per 100 athletes. SRC-related research has also increased; recognition of symptoms that may prolong recovery have been examined, potential biomarkers have been scrutinized, return-to-learn and return-to-play protocols have been developed and honed. However, to date, clinicians and researchers have struggled to find effective interventions to mitigate the significant symptoms after SRC and shorten recovery times. Despite the understood role of the brain as the primary regulator of metabolism, and the well-established metabolic impairments evoked after a concussion, nutrition is often ignored as a core complement to the recovery and rehabilitation process. In this article, we will identify deficiencies and/or inadequacies in nutrients post-concussion and provide support for potential exacerbation of injury and delayed recovery due to inadequate intake of nutrients prior to sustaining an SRC. Additionally, we will discuss the effect of derangement of the metabolic cascade post-concussion, and identify key nutrients, that if supplemented immediately post-injury, could increase neuroprotection, and improve recovery outcomes. Animal and cell culture studies have provided substantial evidence for not only the interrelationship of nutrient adequacy and the adaptation in the metabolic cascade post-concussion on neuroprotection, but also key nutrients that if supplemented immediately post-injury could enhance standard of care with minimal risk.

Inflammation and fibrosis of the bile ducts are the defining pathological characteristics of primary sclerosing cholangitis (PSC). A previously unexplored mechanism for recurrent cholangitis, one of PSC’s most common presentations, is bacterial colonization of the biliary epithelium in the form of biofilm, which may confer resistance to antibiotics and host phagocytic machinery. The aim of the current study was to assess whether bacteria could be seen on the liver explant and whether they organized in the form of biofilm. An explanted PSC liver from a 60-year-old male who suffered from recurrent cholangitis was formalin-fixed, paraffin-embedded and Gram stained. The specimens were observed under light microscopy. Neither bacteria nor biofilm were detected. We did not detect bacteria or biofilm in the liver explant of a single PSC patient with recurrent cholangitis using standard light microscopy. We suspect this may be in part due to techniques related to tissue preservation and microscopy.