Nonalcoholic fatty liver disease (NAFLD) is significantly on the rise, which will seriously affect human health; yet, there is no approved drug for the treatment of NAFLD currently. Recently, more and more studies have demonstrated that intestinal bacteria affect liver function through the gut-liver axis, and that the imbalance of intestinal bacterial composition is essential in the pathogenesis of NAFLD. Correcting intestinal bacterial imbalance, therefore, may prevent the development and attenuate the progression of NAFLD. Fecal microbiota transplantation (FMT) is considered the most effective method to correct intestinal bacteria imbalance, but its therapeutic role in NAFLD has not been established. Moreover, the potential molecular mechanisms of FMT for NAFLD have not been elucidated. This review paper summarizes the currently available experimental and clinical research results on the therapeutic effects of FMT for NAFLD. In addition, the underlying molecular mechanisms are proposed, which would provide theoretical support for FMT as a useful modality for the treatment of NAFLD.

Curcumin is a polyphenol present in turmeric and is credited with anti-inflammatory, antioxidant, and chemoprotective properties. Questions remain surrounding curcumin’s bioavailability and the mechanism by which it may exert neuroprotective effects. Following PRISMA 2009 guidelines, a systematic review was conducted to identify randomized, placebo-controlled trials investigating the effects of curcumin supplementation on cognitive function in older adults (>50 years). Five databases were searched (CINAHL, Cochrane Library, PubMed, SCOPUS, Web of Science) with five studies identified, each using different forms of curcumin and validated cognitive screening measures, meeting inclusion criteria. Curcumin doses ranged from between 90 and 4,000 mg/day, with significant improvements found in three of the five studies. Firstly, the most recent study found improvements with 90 mg of curcumin twice daily in tests of selective reminding (p = 0.002), visual memory (p = 0.01), and attention (p < 0.0001) over 18 months in non-demented individuals. The second study found improvement in Montreal Cognitive Assessment tool with 1,500 mg/day curcumin over 52 weeks (p = 0.02). Another study found improvement in serial three subtraction task responses after 4 weeks compared with the placebo group (p = 0.044). Of the adverse events reported (n = 58), gastrointestinal symptoms were most common (n = 34). Before curcumin can be recommended to treat or reduce rates of cognitive decline, well-designed trials with standardization in dose, method of assessing cognition, and duration, are required to determine the most bioavailable form of curcumin with minimal adverse effects.

Nonalcoholic fatty liver disease (NAFLD) is the accumulation of fat in the liver in the absence of secondary causes. NAFLD is a multifactorial disease that results from the interaction of genetic predisposition and metabolic, inflammatory and environmental factors. Among these factors, dysregulation of gut microbiome has been linked to the development of fatty liver disease. The microbiome composition can be modified by dietary habits leading to gut microbiome dysbiosis, especially when a diet is rich in saturated fats, animal products and fructose sugars. Different species of bacteria in the gut metabolize nutrients differently, triggering different pathways that contribute to the accumulation of fat within the liver and triggering inflammatory cascades that promote liver damage. In this review, we summarize the current understanding of the roles of gut microbiota in mediating NAFLD development and discuss possible gut microbiota-targeted therapies for NAFLD. We summarize experimental and clinical evidence, and draw conclusions on the therapeutic potential of manipulating gut microbiota to decrease the incidence and prevalence of fatty liver disease.

Background and Aims: Rifampicin (RFP) and isoniazid (INH) are widely used as anti-tuberculosis agents. However, the mechanisms underlying the involvement of reactive oxygen species and mitochondria in RFP- and INH-related hepatotoxicity have not been established yet. This study aimed to observe the intracellular mechanisms leading to mitochondrial dysfunction and morphological changes in RFP- and INH-induced hepatocyte injury.

Methods: Cell injury, changes in mitochondrial function, and expression and activation of dynamin related protein 1 (Drp1), known as the main protein for mitochondrial fission, were analyzed in cultured QSG7701 cells exposed to RFP and INH.

Results: INH and RFP treatment induced pronounced hepatocyte injury and increased cell death. In the similar context of aspartate aminotransferase elevation and adenosine triphosphate synthesis decrease, changes in mitochondrial membrane permeability and reactive oxygen species in hepatocytes induced by RFP were significantly different from those induced by INH (p < 0.05). Particularly, we observed the overactivation and mitochondrial translocation of Drp1 in RFP-induced cell injury, which was not occurred with exposure to INH.

Conclusions: RFP-induced hepatotoxicity may be closely related to mitochondrial dysfunction and Drp1-mediated mitochondrial fission.

Orthotopic liver transplantation is the definitive treatment for end-stage liver disease and hepatocellular carcinomas. Biliary complications are the most common complications seen after transplantation, with an incidence of 10–25%. These complications are seen both in deceased donor liver transplant and living donor liver transplant. Endoscopic treatment of biliary complications with endoscopic retrograde cholangiopancreatography (commonly known as ERCP) has become a mainstay in the management post-transplantation. The success rate has reached 80% in an experienced endoscopist’s hands. If unsuccessful with ERCP, percutaneous transhepatic cholangiography can be an alternative therapy. Early recognition and treatment has been shown to improve morbidity and mortality in post-liver transplant patients. The focus of this review will be a learned discussion on the types, diagnosis, and treatment of biliary complications post-orthotopic liver transplantation.

Background and Aims: The management of post-endoscopic variceal ligation (EVL) bleeding ulcers (PEBUs) is currently based on local expertise and patients liver disease status. The present retrospective study investigated associations between the endoscopic morphology of PEBUs and patient outcomes.

Methods: Patients underwent EVL (primary or secondary), from January 2015 to January 2018, in two tertiary care hospitals in India (ILBS New Delhi and Dharamshila Narayana New Delhi). Mortality rates were determined at post-EVL day five and week six. PEBUs were typified based on Jamwal & Sarin classification system as follows: A, ulcer with active spurting; B, ulcer with ooze; C, ulcer base with visible vessel or clot; and D, clean or pigmented base.

Results: Of 3854 EVL procedures, 141 (3.6%) patients developed PEBU, and 46/141 (32.6%) suffered mortality. Among the former, the PEBU types A, B, C, and D accounted for 17.7, 26.2, 36.3, and 19.8%, respectively. Of those who died, 39.1, 30.4, 21.7, and 8.8% had PEBU types A, B, C, and D. Treatments included transjugular intrahepatic portosystemic shunts (TIPS), esophageal self-expandable metal stent (SEMS), glue and sclerosant injection, Sengstaken-Blakemore tube placement and liver transplant. On univariate analysis, no correlation with hepatic venous pressure gradient, TIPS placement, size of varices, or number of bands was found. The Model for End-Stage Liver Disease (MELD)-sodium score correlated positively with outcome. After adjusting for MELD-sodium score, mortality was best predicted by type-A ulcer (p = 0.024; OR 8.95, CI 1.34–59.72).

Conclusions: PEBU occurred in 3.6% of a large EVL cohort. Stratifying patients based on PEBU type can help predict outcomes, independent of the MELD-sodium score. Classifying PEBUs by endoscopic morphology may inform treatment strategies, and warrants further validation.

Hepatic abscesses are an uncommon extra-intestinal manifestation of inflammatory bowel disease, the incidence of which has been estimated to be approximately 7 per 10,000 patients with inflammatory bowel disease. It is unclear whether patients with Crohn’s disease or patients with ulcerative colitis (UC) are at higher risk of developing this complication. Based on case reports, most cases are found in Crohn’s disease; however, a recent cohort study showed an increased risk in UC instead. Hepatic abscesses in the pediatric population are rare, and there have been no reported cases of hepatic abscesses in a pediatric patient with UC. We describe herein a pediatric patient with UC who developed hepatic abscesses and portal vein thrombosis. This patient also had an extended time in remission from his UC despite being off of immunosuppressive therapies, and we speculate on how his clinical course and treatment strategies may have contributed to this.

Compositae species are applied as whole or part of the feed stock for animals and poultry. However, rabbits display varied preferences in their consumption of these plants, following the order of: Melanthera scandens (MS) > Synedrella nodiflora (SN) > Aspilia africana (AA) > Ageratum conyzoides (AC). This preference profile may be due to variation in chemical composition, flavor or toxicity of the plants. The rabbits in our farm feed on 100% MS or SN with excellent performance. This study, therefore, is set to: obtain the methanol extract of these plants, screen them for their antibacterial activity, determine their toxicity and investigate the chemical composition of their n-hexane fraction (volatile constituents).

Crushed leaves of MS, AC, AA and SN were extracted with methanol using soxhlet extraction technique to obtain the methanol extract of each plant. Phytochemical examination, antibacterial activity determination (using the agar-well diffusion technique) and toxicity studies (using experimental white albino mice) were carried out on the methanol extracts. Vacuum liquid chromatography (VLC) fractionation of each extract was carried out. The n-hexane fractions obtained from the VLC fractionation were subjected to gas chromatography-mass spectroscopy (GC-MS) analysis and the chemical constituents were identified.

Phytochemical screening showed the presence of alkaloids, steroids and tannins in all the extracts. The extracts exhibited varying degrees of antibacterial activities against bacterial strains used for this study. AC showed activity against tested microbes, having zones of inhibition ranging from 10 mm and 22 mm, with the exception of Bacillus stearothermophilus and Pseudomonas fluorescens. MS inhibited the growth of the microbes, having zones of inhibition ranging from 12 mm and 20 mm, with the exception of Bacillus anthracis, Bacillus stearothermophilus, Clostridium sporogens and Enterococcus faecalis. AA did not show activity against four of the tested microbes: Bacillus anthracis, Klebsiella pneumonia, Pseudomonas fluorescens and Enterococcus faecalis. SN however, inhibited the growth of all the bacterial strains tested, with the exception of Escherichia coli only. On the other hand, when streptomycin was used as a positive control, the growth of all the bacterial strains was inhibited, having zones of inhibition ranging from 15 mm and 22 mm. Toxicity study showed that the extracts were not toxic at the concentrations of 10 mg/kg through 1,000 mg/kg; however, at higher concentrations of 1,600 mg/kg through 2,500 mg/kg, the extracts became toxic. The LD50 was determined to be 1,275 mg/kg for all the extracts. GC-MS analysis showed the presence of 4-tetradecene in all of the extracts, except AC.

The varied preferences observed in rabbit consumption of these plants definitely have nothing to do with toxicity. The presence of various fatty acids and unsaturated hydrocarbons in the volatile components of the extracts, which influence the flavor, may be responsible for the wellness of rabbits and their relative preferences in consumption.

Background and Aims: Patients with cirrhosis of the liver have high mortality after surgery. We investigated the mortality in patients with cirrhosis of the liver who underwent surgery other than liver transplant and applied the Mayo clinic model to predict mortality and compare with the observed mortality. We also studied the association of the observed mortality with the Child-Turcotte-Pugh (CTP) class and the model for end-stage liver disease (MELD) and model for end-stage liver disease-sodium (MELD-Na) scores.

Methods: The electronic records database of our hospital was accessed to analyze the data of 133 cirrhotic patients who underwent various surgeries under general anesthesia from October 2009 to June 2017. The Mayo risk score was applied to each and used to calculate predicted mortality; the MELD and MELD-Na scores were also calculated. Telephonic interview was performed with the patients and or their relative to ascertain survival or time of death after surgery, when the information was not available from the hospital records.

Results: The all-cause observed mortality rates at postoperative days 30 and 90 and at 1 year were 12%, 20.3% and 26.3% respectively. The area under the receiver operating characteristic curve values for the Mayo model as a predictor of 30-day, 90-day and 1-year mortality were 0.836, 0.828 and 0.744 respectively. Good correlation was seen for observed mortality with CTP class and with MELD and MELD-Na scores.

Conclusions: The Mayo model for predicting postoperative mortality in patients with cirrhosis of the liver demonstrated good correlation in this study. The strength of prediction of mortality by Mayo risk score calculation was similar at postoperative days 30 and 90 but decreased at 1-year after the surgery. Good correlation was seen for the observed mortality with MELD, MELD-Na and CTP scores.

The incidence of hepatocellular carcinoma (HCC) is increasing, with this trend expected to continue to the year 2030. Hepatocarcinogenesis follows a predictable course, which makes adequate identification and surveillance of at-risk individuals central to a successful outcome. Moreover, imaging is central to this surveillance, and ultimately to diagnosis and management. Many liver study groups throughout Asia, North America and Europe advocate a surveillance program for at-risk individuals to allow early identification of HCC. Ultrasound is the most commonly utilized imaging modality. Many societies offer guidelines on how to diagnose HCC. The Liver Image Reporting and Data System (LIRADS) was introduced to standardize the acquisition, interpretation, reporting and data collection of HCC cases. The LIRADS advocates diagnosis using multiphase computed tomography or magnetic resonance imaging (MRI) imaging. The 2017 version also introduces contrast-enhanced ultrasound as a novel approach to diagnosis. Indeed, imaging techniques have evolved to improve diagnostic accuracy and characterization of HCC lesions. Newer techniques, such as T1 mapping, intravoxel incoherent motion analysis and textural analysis, assess specific characteristics that may help grade the tumor and guide management, allowing for a more personalized approach to patient care. This review aims to analyze the utility of imaging in the surveillance and diagnosis of HCC and to assess novel techniques which may increase the accuracy of imaging and determine optimal treatment strategies.

Background and Aims: Accumulated evidence has shown that chronic liver inflammation is one of the main risks of hepatocellular carcinoma (HCC), and E167K variant of the transmembrane 6 superfamily member 2 (TM6SF2) plays an important role in the progression of chronic liver diseases and HCC. The aim of this study was to explore effects of the TM6SF2 E167K variant on expression of the inflammatory cytokines TNF-α, IL-2, IL-6 and IL-8 in the HCC cell line HEPA 1-6.

Methods: HEPA 1-6 cells were infected with lentivirus containing either the TM6SF2 E167K variant or TM6SF2 wild-type, or control plasmids. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were conducted to analyze the expression of the inflammatory cytokines TNF-α, IL-2, IL-6 and IL-8. A t-test was used for statistical analysis.

Results: Compared with the control group and TM6SF2 overexpression group, the relative expression of IL-2 and IL-6 mRNAs were significantly elevated in the TM6SF2 E167K overexpression group (p < 0.05). The relative mRNA expression of IL-8 in the TM6SF2 and TM6SF2 E167K overexpression groups were increased compared to the control group (p < 0.05). No obvious differences were observed for the expression of TNF-α in each group. The expression of TNF-α, IL-2, IL-6 and IL-8 that was tested by western blotting showed the same trends as the qRT-PCR results.

Conclusions: In conclusion, the E167K variant of the TM6SF2 gene could promote the expression of inflammatory cytokines IL-2 and IL-6 in HEPA 1-6 cells, suggesting that the TM6SF2 E167K variant may accelerate the progression of HCC.

Background and Aims: Drug-induced liver injury with autoimmune features (AI-DILI) mimics the clinical presentation, and laboratory and pathologic features of idiopathic autoimmune hepatitis (AIH). We aimed to identify histopathologic hallmarks to differentiate these entities.

Methods: All liver biopsies archived for the past 10 years were reviewed retrospectively to identify cases of recently detected liver injury associated with predominantly lymphoplasmacytic interphase hepatitis, positive markers for liver autoimmunity, and negative tests for viral hepatitis. Twenty cases were divided into AIH (n = 12) or AI-DILI (n = 8) groups. Blind qualitative evaluation of necroinflammatory changes and liver fibrosis were performed according to the Scheuer scoring system. Cellular densities were determined using ImageJ (V1.51t, National Institutes of Health, Bethesda, MD, USA). Fibrosis was assessed on Masson trichrome-stained slides, and collagen deposition was estimated following a protocol of color deconvolution.

Results: Necroinflammatory changes as well as densities (portal and lobular) of neutrophils and eosinophils, intracellular cholestasis, and regenerative changes did not differ between the two groups (P ≥ 0.05). Neutrophil densities but not eosinophils showed a positive correlation with the severity of hepatocellular damage (r = 0.6 and 0.58, vs. alanine aminotransferase, P < 0.05). Ceroid-laden macrophages but not histiocytic aggregates appeared to be more common in AI-DILI (P < 0.05). AIH patients presented more often with evidence of chronic damage, including higher scores of fibrosis and collagen deposition, in comparison to AI-DILI (P < 0.05).

Conclusions: Although there is no histologic feature pathognomonic for AI-DILI or AIH, advanced stages of liver fibrosis can be used to support the diagnosis of AIH in some cases. Definitive diagnosis of AI-DILI requires follow-up and demonstration of complete remission after drug withdrawal with no need for immunosuppression.

Post-stroke depression (PSD) is a common and complex post-stroke neuropsychiatric disorder, which not only delays functional recovery but also increases mortality, and which currently lacks effective drug therapy. The pathogenesis of PSD is associated with impairment of the subcortical neural circuits and alterations of synaptic plasticity and neurotransmitters, but the exact mechanisms of PSD remain unknown. Our previous work indicates that the death-associated protein kinase 1 (DAPK1) mediates neuronal death after stroke. Genetic deletion of DAPK1 gene or blocking DAPK1 signal in the PSD mouse model can not only alleviate cerebral ischemic injury but also relieve PSD-like behaviors. Our previous work has also demonstrated the following results. First, the neural circuit of dorsal CA1 (dCA1) to medial prefrontal cortex (mPFC) (dCA1-mPFC) is selectively impaired after stroke. Second, the DAPK1 signal is involved in the impairment of dCA1-mPFC neural circuit after stroke. Third, genetic deletion of the DAPK1 gene or blocking of the DAPK1 signal alleviates the injury of dCA1-mPFC neural circuit after stroke and improves PSD-like behaviors. In conclusion, we hypothesize that activated DAPK1 signal after stroke induces apoptosis in the hippocampal dCA1 neurons, leading to loss of the dCA1-mPFC glutamatergic projections, synaptic injury, decrease of glutamate release, inhibition of mPFC neurons, and finally onset of PSD. We hope to further replenish the mechanisms of PSD and provide new insights for PSD treatment.

Lambl’s excrescences have a low prevalence in the general population. Although they occur most frequently in adults over 60 years-old, pediatric cases have been described. The cases in adulthood are associated with ischemic stroke, but in childhood they are asymptomatic. The aim of reporting on this case series is to show the association or coexistence of Lambl’s excrescences with some congenital heart diseases (CHDs), of which there are no known descriptive case series in adults or children. We present 17 patients (8 females), with a mean age of 23.7 years; among these cases, 64.7% were under 18 years-old. We found that 94% of the Lambl’s excrescences were located on the aortic valve. In 47% (8 cases), they coincided with a CHD (with 6 of those individuals being under 18 years-old). We propose the hypothesis that Lambl’s excrescences could have a congenital origin or coexist with CHD. No complications were found throughout the follow-up. Lambl’s excrescences could be more frequent than currently reported in the literature, and more research should be done on their significance in CHD-associated stroke.