• liver transplant
• non-alcoholic fatty liver disease
• posttransplant metabolic syndrome
• recurrence

• NAFLD
• de novo malignancies
• liver transplantation
• metabolic syndrome
• post-transplant diabetes mellitus

• NASH
• cryptogenic cirrhosis
• liver transplantation
• metabolic syndrome
• rational immunosuppression

• adult
• humans
• cardiovascular diseases
• cardiovascular diseases/prevention & control
• exercise therapy
• exercise therapy/adverse effects
• fatigue
• fatigue/etiology
• liver transplantation
• liver transplantation/adverse effects
• metabolic syndrome
• metabolic syndrome/complications
• quality of life

• Humans
• Adult
• Liver Transplantation/adverse effects
• Quality of Life
• Cardiovascular Diseases/prevention & control
• Metabolic Syndrome/complications
• Exercise Therapy/adverse effects
• Fatigue/etiology

• hyperoxia
• ischemia–reperfusion injury
• lactate level
• liver transplantation

• Fatty liver
• Liver
• NAFL
• NAFLD
• NASH
• Steatohepatitis
• Survival
• Transplant
• Transplantation

Background: Diagnostic tests for early allograft dysfunction (EAD) after living donor liver transplantation (LDLT) vary widely. We aimed to evaluate the predictive value of rotational thromboelastometry (ROTEM)-derived parameters in EAD. Materials and Methods: A total of 121 patients were reviewed. The definition of EAD proposed by Olthoff et al. included the presence of any of the following at postoperative day 7: bilirubin level ≥ 10 mg/dL, INR ≥ 1.6, or serum AST or ALT levels > 2000 IU/L. All patients underwent ROTEM assay, which consisted of an extrinsically activated thromboelastometric test (EXTEM) before and 24 h after LDLT. Results: The 1-year/2-year OS were 68.%8/64.5% and 94.4%/90.8% for the EAD and non-EAD groups, respectively (p = 0.001). Two independent risks were identified for EAD, the postoperative clotting time (CT, p = 0.026) and time to maximum clot firmness (maximum clot firmness (MCF)-t, p = 0.009) on the EXTEM. CT yielded a specificity of 82.0% and negative predictive value of 83.0%, and MCF-t displayed a specificity of 76.4% and negative predictive value of 81.9% in diagnosing EAD. The use of the 24 h post-LDLT ROTEM increased the effectiveness of predicting overall survival (OS) compared to using the Olthoff’s EAD criteria alone (p < 0.001). Conclusion: We conclude that CT and MCF on EXTEM were independent predictors of EAD. The 24 h post-LDLT ROTEM can be used with conventional laboratory tests to diagnose EAD. It increases the effectiveness of predicting OS.

• coagulation
• early allograft function
• liver transplantation
• rotational thromboelastometry

• Child
• Enzymes
• Liver
• Non-alcoholic fatty liver disease
• Obesity
• Overweight
• Vitamin D

• Interleukin-6 (IL-6)
• Ischemia-reperfusion injury (IRI)
• Mitochondria
• Mitofusion2 (Mfn2)
• Nonalcoholic fatty liver disease (NAFLD)
• Toll-like receptor 4 (TLR4)
• Tumor necrosis factor-α (TNF-α)

• Nonalcoholic steatohepatitis (NASH)
• de novo NASH
• nonalcoholic fatty liver disease (NAFLD)
• recurrent NASH

• NASH
• liver transplantation
• share 35 policy
• united network for organ sharing

• Adult
• Azo Compounds
• Biopsy
• Fatty Liver/diagnosis
• Female
• Frozen Sections/methods
• Humans
• Italy
• Liver Transplantation
• Male
• Staining and Labeling/methods
• Tissue Donors
• Transplantation, Homologous
• Transplants/pathology

Cardiac sarcoidosis (CS) is a rare but potentially life-threatening disease that causes conduction disturbance, systolic dysfunction, and, most notably, sudden cardiac death. ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) plays important roles not only in diagnosing CS but also in evaluating the effects of anti-inflammatory therapy. A volume-based analysis of parameters measured by FDG PET, so-called cardiac metabolic volume (CMV), has emerged as a new assessment tool. CMV is measured as the volume within the boundary determined by a reference tissue such as the liver and the blood pool uptake. However, there is a possibility that oral steroid therapy could lead to variations of the liver and the blood pool uptake. Here, we attempted to evaluate the steroid effects on the liver and the blood pool uptake.

A total of 38 CS patients who underwent FDG PET/CT before and during steroid therapy were retrospectively enrolled. Volumes of interest (VOIs) were placed in the right lobe of the liver and descending aorta (DA). The maximum standardized uptake value (SUVmax), SUVmean, and SUVpeak of the liver and DA were compared between time points before and during steroid therapy.

The SUVmax, SUVmean, and SUVpeak of the liver during steroid therapy significantly increased from the time point before the therapy (SUVmax 3.5 ± 0.4 vs. 3.8 ± 0.6, p = 0.014; SUVmean 2.7 ± 0.3 vs. 3.0 ± 0.5, p = 0.0065; SUVpeak 3.0 ± 0.4 vs. 3.4 ± 0.6, p = 0.006). However, the SUVmax, SUVmean, and SUVpeak in the DA did not significantly change (SUVmax 2.2 ± 0.3 vs. 2.2 ± 0.4, p = 0.46; SUVmean 1.9 ± 0.3 vs. 2.0 ± 0.4, p = 0.56; SUVpeak 2.0 ± 0.3 vs. 2.0 ± 0.3, p = 0.70).

We measured FDG uptake in the liver and blood pool before and during steroid therapy. Steroid therapy increased the liver uptake but not the blood pool uptake. Our findings suggested that the DA uptake is a more suitable threshold than liver uptake to evaluate therapeutic effects using volume-based analysis of cardiac FDG PET.

• 18F-Fluorodeoxyglucose
• Cardiac sarcoidosis
• Metabolic cardiac volume
• PET
• Steroid therapy

• Cohort study
• Non-HDL-c/HDL-c ratio
• Nonalcoholic steatohepatitis

• Adult
• Alanine Transaminase/blood
• Aspartate Aminotransferases/blood
• Biomarkers/blood
• Blood Pressure
• Body Mass Index
• Cholesterol, HDL/blood
• Cholesterol, LDL/blood
• Cohort Studies
• Female
• Humans
• Male
• Middle Aged
• Non-alcoholic Fatty Liver Disease/blood
• Non-alcoholic Fatty Liver Disease/epidemiology
• Risk Factors

• 81670753 National Natural Science Foundation of China
• 2015ZDZX05005 Shandong Provincial Science and Technology Major Project
• 2014WS0425 Shandong Provincial Medical and Health Science and Technology Development Plan
• 2018YT33 The Youth Talent Fund of The Second Hospital of Shandong University

• Liver transplant
• Metabolic syndrome
• Nonalcoholic fatty liver disease
• Nonalcoholic steatohepatitis
• Recurrent NAFLD

• biopsy
• fatty liver
• genotype
• hepatic steatosis
• transplant

Nonalcoholic steatohepatitis (NASH) is a leading indication for liver transplantation (LT). We hypothesized that weight gain after LT may be exacerbated by reduced metabolic rates due to the LT procedure, particularly during exercise. We aimed to compare resting and exercise energy expenditure between patients transplanted for NASH and nontransplant nonalcoholic fatty liver disease (NAFLD) subjects.

NASH LT recipients (>1-year post, n = 14) and NAFLD controls (n = 13) underwent analysis of body composition, resting energy expenditure (REE), and exercise energy expenditure (VO_2max), the latter using a ramped-Bruce protocol assessed by expired gas analysis and peak heart rate.

Participants were mean 61.5 ± 7.9 years, 48.1% men, and 66.7% white. Baseline comorbidities were similar between groups. Among men, mean REE adjusted for total (17.7 vs 18.8, P = 0.87) and lean body mass (23.5 vs 26.9, P = 0.26), as well as VO₂ (20.1 vs 23.9, P = 0.29), was lower in NASH LT recipients compared with NAFLD controls, respectively, although not statistically significant. However, female NASH LT recipients had significantly lower mean REE than NAFLD controls when adjusted for total (14.2 vs 18.9, P = 0.01) and lean body mass (19.3 vs 26.5, P = 0.002), as well as significantly lower VO_2max (14.4 vs 20.6, P = 0.017).

NASH LT recipients, particularly women, have lower REE and exercise energy expenditure compared with nontransplant NAFLD patients. More aggressive diet and exercise programs for post-LT NASH recipients to account for reduced resting and exercise metabolic rates may attenuate weight gain in this vulnerable population.

• Bariatric surgery
• Cirrhosis
• Liver transplantation
• NASH
• Obesity

To evaluate the relationship between the state of transplanted liver graft and the recipient quality of life (QOL) of histologically proven lesions in a 10-year post liver transplantation (LT) cohort of patients.

Seventy-two recipients with a functional first graft at 10 years post-LT underwent liver biopsy and completed a QOL questionnaire. Logistic regression analysis was used to explore associations between histological, clinical and QOL criteria.

Ten years after LT, fibrosis was detected in 53% of patients, and affected the general health perception, while ductopenia, present in 36%, affected the well-being (P = 0.05). Hepatic steatosis (HS) was present in 33% of patients and was associated with the worst QOL score on multiple domains. When compared to patients without HS, patients with HS had significantly higher incidence of fibrosis (P = 0.03), hepatitis C virus (HCV) infection (P = 0.007), and more patients had retired from their job (P = 0.03). Recurrent or de novo HCV-associated fibrosis and patient retirement as objective variables, and abdominal pain or discomfort and joint aches or pains as subjective variables, emerged as independent determinants of HS.

Long-term liver graft lesions, mainly HS presumably as a surrogate marker of HCV infection, may have a substantial impact on QOL 10 years after LT.

• Liver transplantation
• Quality of life
• Liver biopsy
• Hepatic steatosis
• Liver fibrosis

• Donor liver steatosis
• Liver transplantation
• New-onset diabetes after transplantation

• Liver transplantation
• Metabolic syndrome
• Non-alcoholic fatty liver disease
• Non-alcoholic steatohepatitis

• Clinical Decision-Making
• Humans
• Liver Cirrhosis/etiology
• Liver Cirrhosis/mortality
• Liver Cirrhosis/surgery
• Liver Transplantation/mortality
• Non-alcoholic Fatty Liver Disease/complications
• Non-alcoholic Fatty Liver Disease/mortality
• Non-alcoholic Fatty Liver Disease/surgery
• Prognosis
• Risk Assessment
• Treatment Outcome

• MR/L022699/1 Medical Research Council

• Liver transplant
• Non-alcoholic fatty liver disease

• Humans
• Life Style
• Liver/physiopathology
• Liver Transplantation
• Non-alcoholic Fatty Liver Disease/drug therapy
• Non-alcoholic Fatty Liver Disease/pathology
• Non-alcoholic Fatty Liver Disease/surgery
• Risk Factors

• Cirrhosis
• Liver transplantation
• NAFLD
• NASH
• Obesity
• Outcomes
• Review
• Steatosis

Acute liver failure (ALF) is a reversible disorder that is associated with an abrupt loss of hepatic mass, rapidly progressive encephalopathy and devastating complications. Despite its high mortality, an emergency liver transplantation nowadays forms an integral part in ALF management and has substantially improved the outcomes of ALF. Here, we report the case of a 32-year-old female patient who was admitted with grade IV hepatic encephalopathy (coma) following drug-induced ALF. We performed an emergency auxiliary partial orthotopic liver transplantation with a “high risk” graft (liver macrovesicular steatosis approximately 40%) from a living donor. The patient was discharged on postoperative day 57 with normal liver function. Weaning from immunosuppression was achieved 9 mo after transplantation. A follow-up using CT scan showed a remarkable increase in native liver volume and gradual loss of the graft. More than 6 years after the transplantation, the female now has a 4-year-old child and has returned to work full-time without any neurological sequelae.

• Acute liver failure
• Auxiliary partial orthotopic liver transplantation
• Fatty liver graft

• Adult
• Biopsy
• Chemical and Drug Induced Liver Injury/diagnosis
• Chemical and Drug Induced Liver Injury/etiology
• Chemical and Drug Induced Liver Injury/surgery
• Donor Selection
• Fatty Liver/complications
• Fatty Liver/diagnosis
• Female
• Graft Survival
• Humans
• Immunosuppressive Agents/administration & dosage
• Liver Failure, Acute/chemically induced
• Liver Failure, Acute/diagnosis
• Liver Failure, Acute/surgery
• Liver Function Tests
• Liver Regeneration
• Liver Transplantation/adverse effects
• Liver Transplantation/methods
• Living Donors
• Risk Factors
• Time Factors
• Tomography, X-Ray Computed
• Treatment Outcome

Non-alcoholic fatty liver disease (NAFLD) is now the most frequent chronic liver disease that occurs across all age groups and is recognized to occur in 14%-30% of the general population, representing a serious and growing clinical problem due to the growing prevalence of obesity and overweight. Histologically, it resembles alcoholic liver injury but occurs in patients who deny significant alcohol consumption. NAFLD encompasses a spectrum of conditions, ranging from benign hepatocellular steatosis to inflammatory nonalcoholic steatohepatitis, fibrosis, and cirrhosis. The majority of hepatocellular lipids are stored as triglycerides, but other lipid metabolites, such as free fatty acids, cholesterol, and phospholipids, may also be present and play a role in disease progression. NAFLD is associated with obesity and insulin resistance and is considered the hepatic manifestation of the metabolic syndrome, a combination of medical conditions including type 2 diabetes mellitus, hypertension, hyperlipidemia, and visceral adiposity. Confirmation of the diagnosis of NAFLD can usually be achieved by imaging studies; however, staging the disease requires a liver biopsy. Current treatment relies on weight loss and exercise, although various insulin-sensitizing agents, antioxidants and medications appear promising. The aim of this review is to highlight the current information regarding epidemiology, diagnosis, and management of NAFLD as well as new information about pathogenesis, diagnosis and management of this disease.

• Non-alcoholic fatty liver disease
• Non-alcoholic steatohepatitis
• Liver disease

Nonalcoholic fatty liver disease (NAFLD) is characterized by the aberrant accumulation of triglycerides in hepatocytes in the absence of significant alcohol consumption, viral infection or other specific causes of liver disease. NAFLD has become a global health problem, but its pathogenesis remains poorly understood and no efficient pharmaceutical treatments have yet been established. The farnesoid X receptor (FXR) is a member of nuclear receptors of intracellular ligand-activated transcription factors and plays an important role in metabolism of bile acids, lipid and glucose. In addition, it has been recently reported that FXR participates in regulating insulin resistance and lipid metabolic disorder, inhibiting the activation of hepatic stellate cells and penetration of inflammatory cells, and promoting the enterohepatic circulation and regeneration of liver cells to defer liver fibrosis, which is significant for NAFLD. Several FXR agonists have been identified and proved to be optimistic in preventing and treating NAFLD both experimentally and clinically, indicating that FXR may be a therapeutic target for NAFLD. The use of FXR in NAFLD remains controversial currently.

• BAs
• Nonalcoholic fatty liver disease
• Farnesoid X receptor
• FXR agonist

AIM: To study at what temperature the oxygen carried by the perfusate meets liver requirements in a model of organ perfusion.

METHODS: In this study, we correlated hypoxia inducible factor (HIF)-1α expression to the perfusion temperature and the hepatic oxygen uptake in a model of isolated perfused rat liver. Livers from Wistar rats were perfused for 6 h with an oxygenated medium at 10, 20, 30 and 37 °C. Oxygen uptake was measured by an oxygen probe; lactate dehydrogenase activity, lactate release and glycogen were measured spectrophotometrically; bile flow was gravitationally determined; pH of the perfusate was also evaluated; HIF-1α mRNA and protein expression were analyzed by real time-polymerase chain reaction and ELISA, respectively.

RESULTS: Livers perfused at 10 and 20 °C showed no difference in lactate dehydrogenase release after 6 h of perfusion (0.96 ± 0.23 vs 0.93 ± 0.09 mU/min per g) and had lower hepatic damage as compared to 30 and 37 °C (5.63 ± 0.76 vs 527.69 ± 45.27 mU/min per g, respectively, Ps < 0.01). After 6 h, tissue ATP was significantly higher in livers perfused at 10 and 20 °C than in livers perfused at 30 and 37 °C (0.89 ± 0.06 and 1.16 ± 0.05 vs 0.57 ± 0.09 and 0.33 ± 0.08 nmol/mg, respectively, Ps < 0.01). No sign of hypoxia was observed at 10 and 20 °C, as highlighted by low lactate release respect to livers perfused at 30 and 37 °C (121.4 ± 12.6 and 146.3 ± 7.3 vs 281.8 ± 45.3 and 1094.5 ± 71.7 nmol/mL, respectively, Ps < 0.02), and low relative HIF-1α mRNA (0.40 ± 0.08 and 0.20 ± 0.03 vs 0.60 ± 0.20 and 1.47 ± 0.30, respectively, Ps < 0.05) and protein (3.72 ± 0.16 and 3.65 ± 0.06 vs 4.43 ± 0.41 and 6.44 ± 0.82, respectively, Ps < 0.05) expression.

CONCLUSION: Livers perfused at 10 and 20 °C show no sign of liver injury or anaerobiosis, in contrast to livers perfused at 30 and 37 °C.

• Anaerobiosis
• Hypoxia inducible factor-1α
• Ischemia
• Liver transplantation
• Machine perfusion

• Animals
• Cold Temperature
• Energy Metabolism
• Glycogen/metabolism
• Hypoxia-Inducible Factor 1, alpha Subunit/genetics
• Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
• In Vitro Techniques
• L-Lactate Dehydrogenase/metabolism
• Lactic Acid/metabolism
• Liver/drug effects
• Liver/metabolism
• Liver/pathology
• Male
• Organ Preservation/adverse effects
• Organ Preservation/methods
• Organ Preservation Solutions/metabolism
• Organ Preservation Solutions/pharmacology
• Oxygen/metabolism
• Perfusion/adverse effects
• Perfusion/methods
• RNA, Messenger/metabolism
• Rats, Wistar
• Reperfusion Injury/etiology
• Reperfusion Injury/metabolism
• Reperfusion Injury/pathology
• Reperfusion Injury/prevention & control
• Time Factors
• Tissue Survival

We demonstrate that caffeine could improve HED-induced hepatic steatosis by promoting lipid metabolism via the cAMP/CREB/SIRT3/AMPK/ACC pathway. SIRT3 acts as a molecular bridge connecting caffeine and lipid metabolism.

• liver transplantation
• obesity

• living donor liver transplantation
• non-alcoholic fatty liver disease
• non-alcoholic steatohepatitis

Graft steatosis is a risk factor for poor initial function after liver transplantation. Biliary complications are frequent even after normal liver transplantation. A subnormothermic machine perfusion (MP20) preservation procedure was developed by our group with high potential for reducing injury to hepatocytes and sinusoidal cells of lean and fatty livers respect to conventional cold storage (CS). We report the response of the biliary tree to CS or MP20, in lean and obese Zucker rat liver. Dipeptidylpeptidase-IV (DPP-IV), crucial for the inactivation of incretins and neuropeptides, was used as a marker. Liver morphology and canalicular network of lean livers were similar after CS/reperfusion or MP20/reperfusion. CS preservation of fatty livers induced serious damage to the parenchyma and to the canalicular activity/ expression of DPP-IV, whereas with MP20 the morphology and canalicular network were similar to those of untreated lean liver. CS and MP20 had similar effects on DPP-IV activity and expression in the upper segments of the intrahepatic biliary tree of fatty livers. DPP-IV expression was significantly increased after MP20 respect to CS or to the controls, both for lean and obese animals. Our data support the superiority of MP20 over CS for preserving fatty livers. Dipeptidylpeptidase-IV activity and expression reveal decreased damage to the intrahepatic biliary tree in fatty livers submitted to subnormothermic machine-perfusion respect to conventional cold storage.

Oxidative stress in fatty livers is mainly generated by impaired mitochondrial β-oxidation, inducing tissue damages and disease progression. Under suitable excitation, light liver endogenous fluorophores can give rise to autofluorescence (AF) emission, the properties of which depend on the organ morphofunctional state. In this work, we characterized the AF properties of a rat liver model of lipid accumulation and oxidative stress, induced by a 1–9-week hypercaloric methionine-choline deficient (MCD) diet administration. The AF analysis (excitation at 366 nm) was performed in vivo, via fiber optic probe, or ex vivo. The contribution of endogenous fluorophores involved in redox reactions and in tissue organization was estimated through spectral curve fitting analysis, and AF results were validated by means of different histochemical and biochemical assays (lipids, collagen, vitamin A, ROS, peroxidised proteins, and lipid peroxidation -TBARS-, GSH, and ATP). In comparison with the control, AF spectra changes found already at 1 week of MCD diet reflect alterations both in tissue composition and organization (proteins, lipopigments, and vitamin A) and in oxidoreductive pathway engagement (NAD(P)H, flavins), with a subsequent attempt to recover redox homeostasis. These data confirm the AF analysis potential to provide a comprehensive diagnostic information on negative effects of oxidative metabolism alteration.

• biopsy
• hepatic steatosis
• histology
• steatohepatitis
• steatosis
• transplant