Over the past years, the global burden of chronic liver diseases (CLDs) has been steadily increasing, irrespective of
age, sex, region, or race. The European Union (EU) countries have the highest ...CLDs burden in the world, with almost 30 million people suffering from CLDs (1,2). Unrecognized and often untreated, CLDs may progress to more
advanced stages, such as cirrhosis, liver failure, and hepatocellular carcinoma (HCC). Global and country-specific estimates of the disability-adjusted life years and years of life
lost place cirrhosis within the top 20 causes (1)
Aim To compare the long-term outcomes between liver transplant (LT) recipients with hepatocellular carcinoma (HCC) who were downstaged with transarterial-chemoembolization (TACE) to the Milan ...criteria (MC) and those initially meeting the MC. Methods This retrospective study enrolled 198 patients with HCC: 38 were downstaged and 160 patients initially met the MC. Post-LT survival and HCC recurrence-free survival were evaluated. We assessed the association of death and HCC recurrence with TACE, baseline (age, sex, disease etiology, Model of End-stage Liver Disease, tumor number and the sum of maximum tumor diameters, waiting time, alpha-fetoprotein level) and explant characteristics (tumor number and the sum of maximum tumor diameters, micro- and macrovascular invasion). Results The recipient survival rates one, three, and five years after LT were 88.2%, 80.1%, and 75.9%, respectively. HCC recurrence-free probabilities were 92.3%, 87.9%, and 85%, respectively. The outcomes were comparable between the groups. In multivariate analysis, the number of tumors on the explant, age, and tumor recurrence were independent risk factors for death. Only the sum of maximum tumor diameters on the explant was an independent risk factor for HCC recurrence. Conclusions Patients successfully downstaged with TACE to the MC can achieve post-LT recipient and HCC recurrence-free survival comparable with patients initially within the MC. Good response to TACE as a criterion for LT may be a method of selecting patients with favorable biological characteristics.
BackgroundHepatocellular carcinoma (HCC) is one of the leading indications for liver transplantation (LT) however, selection criteria remain controversial. We aimed to identify survival factors and ...predictors for tumour recurrence using machine learning (ML) methods. We also compared ML models to the Cox regression model. MethodsThirty pretransplant donor and recipient general and tumour specific parameters were analysed from 170 patients who underwent orthotopic liver transplantation for HCC between March 2013 and December 2019 at the University Hospital Merkur, Zagreb. Survival rates were calculated using the Kaplan-Meier method and multivariate analysis was performed using the Cox proportional hazards regression model. Data was also processed through Coxnet (a regularized Cox regression model), Random Survival Forest (RSF), Survival Support Vector Machine (SVM) and Survival Gradient Boosting models, which included pre-processing, variable selection, imputation of missing data, training and cross-validation of the models. The cross-validated concordance index (CI) was used as an evaluation metric and to determine the best performing model. ResultsKaplan-Meier curves for 5-year survival time showed survival probability of 80% for recipient survival and 82% for graft survival. The 5-year HCC recurrence was observed in 19% of patients. The best predictive accuracy was observed in the RSF model with CI of 0.72, followed by the Survival SVM model (CI 0.70). Overall ML models outperform the Cox regression model with respect to their limitations. Random Forest analysis provided several relevant outcome predictors: alpha fetoprotein (AFP), donor C-reactive protein (CRP), recipient age and neutrophil to lymphocyte ratio (NLR). Cox multivariate analysis showed similarities with RSF models in identifying detrimental variables. Some variables such as donor age and number of transarterial chemoembolization treatments (TACE) were pointed out, but these were not influential in our RSF model. ConclusionsUsing ML methods in addition to classical statistical analysis, it is possible to develop sufficient prognostic models, which, compared to established risk scores, could help us quantify survival probability and make changes in organ utilization.
Fibroblast growth factor 23 (FGF23) has been casually linked to numerous hypophosphatemic bone diseases, however connection with bone loss or fragility fractures is still a matter of debate. The ...purpose of this review is to explore and summarise the known actions of FGF23 in various pathological bone conditions. Besides implication in bone mineralisation, elevated FGF23 showed a pathological effecton bone remodelling, primarily by inhibiting osteoblast function. Unlike the weak association with bone mineral density, high values of FGF23 have been connected with fragility fracture prevalence. This review shows that its effects on bone are concomitantly present on multiple levels, affecting both qualitative and quantitative part of bone strength, eventually leading to impaired bone strength and increased tendency of fractures. Recognising FGF23 as a risk factor for the development of bone diseases and correcting its levels could lead to the reduction of morbidity and mortality in specific groups of patients.
•Chronic liver disease and hepatic osteodystrophy have detrimental impact on bone strength.•Liver transplant candidates showed high prevalence of spinal fragility fractures.•Combination of standard ...X-ray imaging and DXA is needed for adequate bone evaluation in pretransplant period.•Bone specific alkaline phosphatase could be useful for detecting hepatic osteodystrophy in liver transplant candidates.
Existing data on fragility spinal fractures prevalence in liver transplant candidates are scarce and inconsistent. This may be due to other comorbidities, besides hepatic osteodystrophy (HO), that contribute to bone loss and fragility fracture prevalence in chronic liver disease (CLD).
The aim of this study was to investigate the prevalence of spinal thoracic and lumbar fragility fractures among cirrhotic, non-chronic kidney disease (CKD), non-diabetic liver transplant candidates and to explore their relationship with clinical characteristics, laboratory markers and dual-energy x-ray absorptiometry (DXA) results.
This cross-sectional observational study was conducted at Merkur University Hospital, Croatia, between February 2019 and May 2023. Adult patients with liver cirrhosis referred for liver transplantation were included. Patients with acute infection, CKD, diabetes mellitus, malignancies, inflammatory bone diseases and those on corticosteroid or antiresorptive therapy were excluded. Clinical, laboratory and radiological assessment was carried out and patients were accordingly allocated into non-fractured and fractured group for the purpose of statistical analysis.
A total of 90 patients were included in the study. There was 123 fractures, 87 (70.7 %) in the thoracic and 36 (29.3 %) in the lumbar region. Eighty-nine (72.4 %) fractures were grade 1, 31 (25.2 %) were grade 2 and 3 (2.4 %) were grade 3. Patients in the fractured group were significantly older (p < 0.001). No significant differences between fractured and non-fractured group according to laboratory and DXA parameters were noted. Subgroup with lumbar fractures had significantly lower bone mineral density values at L1-L4 region. Statistically significant negative correlation between bone specific alkaline phosphatase (BALP) and hip total BMD (rho = -0.414, p < 0.001) and spine total BMD (rho = -0.258, p = 0.014) values was found.
Present study confirmed detrimental impact of CLD and HO on bone strength. DXA measurement correlated with the presence of lumbar fragility fractures. A combination of standard X-ray imaging and DXA is needed for adequate bone evaluation in pretransplant period and BALP could be useful for detecting HO in CLD. Searching for other risk factors and implementing bone turnover markers and additional imaging techniques for bone loss evaluation in liver transplant candidates is needed.
Neuroendocrine tumors (NET) are a rare and heterogeneous group of neoplasms with variable biological behavior. They frequently metastasize to the liver, requiring active, multimodality treatment. ...Surgical resection, possible in only a minority of cases, was until recently the only potentially curative option. For unresectable NET with liver metastases, liver transplantation (LT) emerged as a potential curative treatment due to relatively slow growth and indolent behavior of the metastases. In this case series with literature review, we retrospectively analyzed the characteristics of 12 highly selected patients with metastatic NET disease as an indication for LT treated in our center. We also summarized the proposed prognostic factors, and evaluated and compared the existing selection criteria. The main poor prognostic factors in our patients were high grade NET and primary tumor in the pancreas. Inconsistent liver transplantation outcome parameters make it difficult to standardize patient selection criteria. There is a need for further studies that would fully elucidate the curative potential of LT in patients diagnosed with NET.
Nonalcoholic fatty liver disease (NAFLD) is a term describing excessive accumulation of fat in hepatocytes, and is associated with metabolic syndrome and insulin resistance. NAFLD prevalence is on ...increase and goes in parallel with the increasing prevalence of metabolic syndrome and its components. That is why Croatian guidelines have been developed, which cover the screening protocol for patients with NAFLD risk factors, and the recommended diagnostic work-up and treatment of NAFLD patients. NAFLD screening should be done in patients with type 2 diabetes mellitus, or persons with two or more risk factors as part of metabolic screening, and is carried out by noninvasive laboratory and imaging methods used to detect fibrosis. Patient work-up should exclude the existence of other causes of liver injury and determine the stage of fibrosis as the most important factor in disease prognosis. Patients with initial stages of fibrosis continue to be monitored at the primary healthcare level with the management of metabolic risk factors, dietary measures, and increased physical activity. Patients with advanced fibrosis should be referred to a gastroenterologist/hepatologist for further treatment, monitoring, and detection and management of complications.
In addition to its antimicrobial protective role, the gut microbiota affects human metabolism and immunity as well
as inflammatory and neuro-hormonal responses. Due to its
beneficial effects on ...health even up to the genetic level, it
is referred to as a “forgotten organ,” “virtual organ,” or “other
brain” (1). The human gut microbiome differs among individuals and usually does not change over time. Its composition is affected by several environmental factors (1-3).
Fecal microbiota transplantation (FMT) or bacteriotherapy
(health donor stool transplantation) is the instillation of a
fecal suspension taken from a healthy donor into the upper or lower gastrointestinal (GI) tract of a patient, with an
aim to enrich and normalize his or her gut microbiota. Although the method has been known for centuries, interest
in it has significantly grown over the last few decades. The
two main reasons are the global epidemic of Clostridioides
difficile (CDI) infection and an improved knowledge of the
GI microbiome and its involvement in various conditions. It
seems that FMT may also transfer host phenotype
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