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Viruses Apr 2024The treatment of hepatitis C virus (HCV) with direct-acting antivirals (DAA) leads to high sustained virological response (SVR) rates, but hepatocellular carcinoma (HCC)...
The treatment of hepatitis C virus (HCV) with direct-acting antivirals (DAA) leads to high sustained virological response (SVR) rates, but hepatocellular carcinoma (HCC) risk persists in people with advanced liver disease even after SVR. We weighted the HCC risk in people with cirrhosis achieving HCV eradication through DAA treatment and compared it with untreated participants in the multicenter prospective Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. Propensity matching with inverse probability weighting was used to compare DAA-treated and untreated HCV-infected participants with liver cirrhosis. Kaplan-Meier analysis and competing risk regression analysis were performed. Within the first 36 months, 30 de novo HCC cases occurred in the untreated group ( = 307), with a weighted incidence rate of 0.34% (95%CI: 0.23-0.52%), compared to 63 cases among SVR patients ( = 1111), with an incidence rate of 0.20% (95%CI: 0.16-0.26%). The 12-, 24-, and 36-month HCC weighted cumulative incidence rates were 6.7%, 8.4%, and 10.0% in untreated cases and 2.3%, 4.5%, and 7.0% in the SVR group. Considering death or liver transplantation as competing events, the untreated group showed a 64% higher risk of HCC incidence compared to SVR patients (SubHR 1.64, 95%CI: 1.02-2.62). Other variables independently associated with the HCC occurrence were male sex, increasing age, current alcohol use, HCV genotype 3, platelet count ≤ 120,000/µL, and albumin ≤ 3.5 g/dL. In real-life practice, the high efficacy of DAA in achieving SVR is translated into high effectiveness in reducing the HCC incidence risk.
Topics: Humans; Carcinoma, Hepatocellular; Male; Antiviral Agents; Female; Liver Neoplasms; Middle Aged; Propensity Score; Aged; Incidence; Sustained Virologic Response; Hepacivirus; Hepatitis C, Chronic; Liver Cirrhosis; Prospective Studies; Italy; Risk Factors; Cohort Studies; Adult
PubMed: 38793565
DOI: 10.3390/v16050682 -
Journal of Personalized Medicine May 2024This Editorial precedes the Special Issue entitled "Novel Challenges and Therapeutic Options for Liver Diseases". Following a historical outline of the roots of...
This Editorial precedes the Special Issue entitled "Novel Challenges and Therapeutic Options for Liver Diseases". Following a historical outline of the roots of hepatology, we provide a brief insight into our colleagues' contributions in this issue on the current developments in this discipline related to the prevention of liver diseases, the metabolic dysfunction-associated steatotic liver disease (or non-alcoholic fatty liver disease, respectively), liver cirrhosis, chronic viral hepatitides, acute-on-chronic liver failure, liver transplantation, the liver-microbiome axis and microbiome transplantation, and telemedicine. We further add some topics not covered by the contributions herein that will likely impact future hepatology. Clinically, these comprise the predictive potential of organokine crosstalk and treatment options for liver fibrosis. With regard to promising developments in basic research, some current findings on the genetic basis of metabolism-associated chronic liver diseases, chronobiology, metabolic zonation of the liver, aspects of the aging liver against the background of demography, and liver regeneration will be presented. We expect machine learning to thrive as an overarching topic throughout hepatology. The largest study to date on the early detection of liver damage-which has been kicked off on 1 March 2024-is highlighted, too.
PubMed: 38793074
DOI: 10.3390/jpm14050492 -
Journal of Clinical Medicine May 2024Treatment of established portal vein narrowing after living donor hepatectomy is challenging. We aimed to present a new approach termed the "elbow patch reconstruction...
Treatment of established portal vein narrowing after living donor hepatectomy is challenging. We aimed to present a new approach termed the "elbow patch reconstruction technique" to correct the narrowed remnant portal vein just or late after right lobe living donor hepatectomy. Demographic and clinical data of 12 living liver donors with narrowed remnant portal veins and treated with the "elbow patch reconstruction technique" were prospectively collected and retrospectively evaluated. Anatomic variation of the portal vein was defined in accordance with the Nakamura classification; six of the living liver donors had type A, three had type B, and the remaining three had type C. In eight of the living liver donors with a narrowed remnant portal vein, diagnosis was detected by intraoperative Doppler ultrasonography and visual inspection by experienced transplant surgeons in the living donor hepatectomy procedure. In the remaining four living liver donors, diagnosis was performed postoperatively when elevation of liver enzymes was noticed during the routine liver function test and Doppler US. The diagnosis was confirmed by multidetector computed tomography. Data from nine males and three females aged 18 to 54 years were analyzed. All of the living liver donors were followed up for a median of 1710 days (min-max: 1178-4447 days; IQR: 1516 days), and none of the living liver donors had any structural or functional complications in the portal vein. Narrowing remnant portal veins are rare, but they are a life-threatening complication in living liver donors, and this condition requires urgent management. Image guided interventions and narrowed segment resection with end-to-end anastomosis using a vascular graft carried a potential risk for thrombosis and restenosis. To avoid these complications, we shared a technique named "elbow patch reconstruction technique". This technique can be very effective in relieving the narrowing of the remnant portal vein after right lobe living donor hepatectomy.
PubMed: 38792466
DOI: 10.3390/jcm13102924 -
Journal of Clinical Medicine May 2024Peritoneal sclerosis (PS) and its most severe form, encapsulating PS (EPS), are rare entities that can occur in various procedures (liver transplantation,...
Peritoneal sclerosis (PS) and its most severe form, encapsulating PS (EPS), are rare entities that can occur in various procedures (liver transplantation, intraperitoneal chemotherapy) or secondary to medications (beta-blockers); however, PS or EPS typically occur in patients undergoing peritoneal dialysis as a form of renal function substitution. Medical or surgical treatments can be applied, but morbidity and mortality have high rates. This condition typically presents clinically as an intestinal obstruction caused by the inclusion of the intestinal loops in the peritoneal fibrous membrane. : Herein, we present data from a single tertiary surgery center that has dedicated teams for patients receiving dialysis. Over 12 years, we analyzed a group of 63 patients admitted for catheter replacement/removal or for acute surgical pathology. In five cases (7.9%), we diagnosed EPS. Two patients with EPS presented with atypical abdominal pathologies requiring emergency surgery: one case of hemoperitoneum caused by a ruptured ovarian cyst and one case of uterine fibroids and metrorrhagia. : The definitive diagnoses were established intraoperatively and by analyzing the morpho-pathological changes in the peritoneum. The possible intraoperative challenges included laborious dissection, difficulties in restoring the correct anatomical landmarks, an increased duration of the surgical intervention and a high rate of incidents and accidents. : The aim of the present study was to emphasize the possibility of other surgical pathologies overlapping with EPS, increasing the complexity of the surgical intervention.
PubMed: 38792461
DOI: 10.3390/jcm13102921 -
Journal of Clinical Medicine May 2024: Hepatic dysfunction (HD) after liver transplantation (LT) or extended hepatic resection (EHR) is associated with graft failure and high short-term mortality. We...
: Hepatic dysfunction (HD) after liver transplantation (LT) or extended hepatic resection (EHR) is associated with graft failure and high short-term mortality. We evaluated the safety and depurative efficacy of CytoSorb® in these settings. The primary endpoint was the change in serum total bilirubin at the end of the treatment compared to the baseline value. The secondary endpoint was to evaluate the trend of serum total bilirubin and coagulation parameters up to 72 h after discontinuation of CytoSorb®. The effects of CytoSorb® therapy on the degree of hepatic encephalopathy (HE), Sequential Organ Failure Assessment (SOFA), and Model for End-Stage Liver Disease (MELD) scores as well as the hemodynamic status compared to baseline were also assessed. : Adult patients with a serum total bilirubin level > 10 mg/dL admitted to the Intensive Care Unit were included. Exclusion criteria were hemodynamic instability, postoperative bleeding and platelet count < 20,000/mm3. : Seven patients were treated. Serum total bilirubin was significantly reduced at the end of treatment. However, seventy-two hours after the discontinuation of extracorporeal therapy, bilirubin levels returned to baseline levels in four patients. A decrease in platelet count was found during therapy, and platelet transfusion was required in six cases. A significant increase in D-dimer at the end of treatment was detected. HE degree, SOFA and MELD scores remained stable, while a deterioration in hemodynamic status was observed in two cases. : Our preliminary findings did not show the possible benefits of CytoSorb in rebalancing clinical and laboratory parameters in patients with HD after LT or EHR.
PubMed: 38792395
DOI: 10.3390/jcm13102853 -
Cancers May 2024Despite the ongoing trend of increasing donor ages in liver transplantation (LT) setting, a notable gap persists in the availability of comprehensive guidelines for the...
BACKGROUND
Despite the ongoing trend of increasing donor ages in liver transplantation (LT) setting, a notable gap persists in the availability of comprehensive guidelines for the utilization of organs from elderly donors. This study aimed to evaluate the viability of livers grafts from donors aged ≥85 years and report the post-LT outcomes compared with those from "ideal" donors under 40 years old.
METHODS
Conducted retrospectively at a single center from 2005 to 2023, this study compared outcomes of LTs from donors aged ≥85 y/o and ≤40 y/o, with the propensity score matching to the recipient's gender, age, BMI, MELD score, redo-LT, LT indication, and cause of donor death.
RESULTS
A total of 76 patients received grafts from donors ≥85 y/o and were compared to 349 liver grafts from donors ≤40 y/o. Prior to PSM, the 5-year overall survival was 63% for the elderly group and 77% for the young group ( = 0.002). After PSM, the 5-year overall survival was 63% and 73% ( = 0.1). A nomogram, developed at the time of graft acceptance and including HCC features, predicted 10-year survival after LT using a graft from a donor aged ≥85.
CONCLUSIONS
In the context of organ scarcity, elderly donors emerge as a partial solution. Nonetheless, without proper selection, LT using very elderly donors yields inferior long-term outcomes compared to transplantation from very young donors ≤40 y/o. The resulting nomogram based on pre-transplant criteria allows for the optimization of elderly donor/recipient matching to achieve satisfactory long-term results, in addition to traditional matching methods.
PubMed: 38791881
DOI: 10.3390/cancers16101803 -
International Journal of Molecular... May 2024Acute kidney injury (AKI) is common following liver transplantation and is associated with liver ischeamia reperfusion (IR) injury. The purpose of this study was to use...
Acute kidney injury (AKI) is common following liver transplantation and is associated with liver ischeamia reperfusion (IR) injury. The purpose of this study was to use a mouse model of liver IR injury and AKI to study the role of Neutrophil Gelatinase Associated Lipocalin (NGAL), a biomarker of AKI, in liver IR injury and AKI. We demonstrate an adapted, reproducible model of liver IR injury and AKI in which remote ischemic preconditioning (RIPC) by repeated episodes of hindleg ischemia prior to liver IR reduced the severity of the IR injury. In this model, serum NGAL at 2 h post reperfusion correlated with AKI development early following IR injury. This early rise in serum NGAL was associated with hepatic but not renal upregulation of NGAL mRNA, suggesting NGAL production in the liver but not the kidney in the early phase post liver IR injury.
Topics: Animals; Acute Kidney Injury; Lipocalin-2; Reperfusion Injury; Ischemic Preconditioning; Mice; Liver; Disease Models, Animal; Male; Kidney; Biomarkers; Mice, Inbred C57BL
PubMed: 38791106
DOI: 10.3390/ijms25105061 -
Biomedicines Apr 2024Recent studies of Cardiovascular-Kidney-Metabolic Syndrome (CKMS) indicate that elevated concentrations of derivatives of phospholipids (ceramide, sphingosine), oxidized... (Review)
Review
Recent studies of Cardiovascular-Kidney-Metabolic Syndrome (CKMS) indicate that elevated concentrations of derivatives of phospholipids (ceramide, sphingosine), oxidized LDL, and lipoproteins (a, b) are toxic to kidney and heart function. Energy production for renal proximal tubule resorption of critical fuels and electrolytes is required for homeostasis. Cardiac energy for ventricular contraction/relaxation is preferentially supplied by long chain fatty acids. Metabolism of long chain fatty acids is accomplished within the cardiomyocyte cytoplasm and mitochondria by means of the glycolytic, tricarboxylic acid, and electron transport cycles. Toxic lipids and excessive lipid concentrations may inhibit cardiac function. Cardiac contraction requires calcium movement from the sarcoplasmic reticulum from a high to a low concentration at relatively low energy cost. Cardiac relaxation involves calcium return to the sarcoplasmic reticulum from a lower to a higher concentration and requires more energy consumption. Diastolic cardiac dysfunction occurs when cardiomyocyte energy conversion is inadequate. Diastolic dysfunction from diminished ATP availability occurs in the presence of inadequate blood pressure, glycemia, or lipid control and may lead to heart failure. Similar disruption of renal proximal tubular resorption of fuels/electrolytes has been found to be associated with phospholipid (sphingolipid) accumulation. Elevated concentrations of tissue oxidized low-density lipoprotein cholesterols are associated with loss of filtration efficiency at the level of the renal glomerular podocyte. Macroscopically excessive deposits of epicardial and intra-nephric adipose are associated with vascular pathology, fibrosis, and inhibition of essential functions in both heart and kidney. Chronic triglyceride accumulation is associated with fibrosis of the liver, cardiac and renal structures. Successful liver, kidney, or cardiac allograft of these vital organs does not eliminate the risk of lipid toxicity. Lipid lowering therapy may assist in protecting vital organ function before and after allograft transplantation.
PubMed: 38790940
DOI: 10.3390/biomedicines12050978 -
BMC Infectious Diseases May 2024The recently used pan-immune-inflammation value (PIV) has not been adequately studied as a predictive marker for mortality in immunosuppressed patients. The aim of this...
BACKGROUND
The recently used pan-immune-inflammation value (PIV) has not been adequately studied as a predictive marker for mortality in immunosuppressed patients. The aim of this study was to evaluate the usefulness of baseline PIV level as a predictor of 30-day mortality in solid organ transplant (SOT) recipients with gram negative bloodstream infections (GN-BSI).
METHODS
This retrospective, cross-sectional study was conducted between January 1, 2019, and December 31, 2022, in 1104 SOT recipients. During the study period, 118 GN-BSI were recorded in 113 patients. Clinical, epidemiological, and laboratory data were collected, and mortality rates (30-day and all-cause) were recorded.
RESULTS
The 113 recipients had a median age of 50 years [interquartile range (IQR) 37.5-61.5 years] with a male predominance (n = 72, 63.7%). The three most common microorganisms were as follows: 46 isolates (38.9%) of Escherichia coli, 41 (34.7%) of Klebsiella pneumoniae, and 12 (10.2%) of Acinetobacter baumannii. In 44.9% and 35.6% of the isolates, production of extended-spectrum beta-lactamases and carbapenem resistance were detected, respectively. The incidence of carbapenem-resistant GN-BSI was higher in liver recipients than in renal recipients (n = 27, 69.2% vs n = 13, 17.6%, p < 0.001). All-cause and 30-day mortality rates after GN-BSI were 26.5% (n = 30), and 16.8% (n = 19), respectively. In the group with GN-BSI-related 30-day mortality, the median PIV level was significantly lower (327.3, IQR 64.8-795.4 vs. 1049.6, IQR 338.6-2177.1; p = 0.002). The binary logistic regression analysis identified low PIV level [hazard ratio (HR) = 0.93, 95% confidence interval (CI) 0.86-0.99; p = 0.04], and increased age (HR = 1.05, 95% CI 1.01-1.09; p = 0.002) as factors associated with 30-day mortality. The receiver operating characteristic analysis revealed that PIV could determine the GN-BSI-related 30-day mortality with area under curve (AUC): 0.723, 95% CI 0.597-0.848, p = 0.0005.
CONCLUSIONS
PIV is a simple and inexpensive biomarker that can be used to estimate mortality in immunosuppressed patients, but the results need to be interpreted carefully.
Topics: Humans; Middle Aged; Male; Female; Retrospective Studies; Adult; Cross-Sectional Studies; Gram-Negative Bacterial Infections; Bacteremia; Organ Transplantation; Transplant Recipients; Inflammation; Gram-Negative Bacteria; Immunocompromised Host
PubMed: 38789916
DOI: 10.1186/s12879-024-09413-x -
Revista de Gastroenterologia de Mexico... May 2024Hepatocellular carcinoma (HCC) is a primary malignant tumor of liver epithelial cells and is the most frequent primary liver cancer. The broadening of transplantation...
INTRODUCTION AND AIMS
Hepatocellular carcinoma (HCC) is a primary malignant tumor of liver epithelial cells and is the most frequent primary liver cancer. The broadening of transplantation and resectability criteria has made therapeutic decisions more complex. Our aim was to describe the clinical and survival characteristics of patients with HCC treated through resection or liver transplantation at our hospital and identify the presence of factors that enable outcome prediction and facilitate therapeutic decision-making.
MATERIALS AND METHODS
Patients with HCC that underwent surgery with curative intent at the Hospital Universitario Marqués de Valdecilla, within the time frame of 2007 and 2017, were retrospectively identified. Survival, mortality, disease-free interval, and different outcome-related variables were analyzed.
RESULTS
Ninety-six patients with a mean follow-up after surgery of 44 months were included. Overall mortality and recurrence were higher in the resection group. Mean survival was 51.4 months in the liver transplantation group and 37.5 months in the resection group, and the disease-free interval was 49.4 ± 37.2 and 27.4 ± 28.7 months, respectively (p = 0.002). The tumor burden score was statistically significant regarding risk for recurrence and specific mortality.
CONCLUSIONS
There appears to be no patient subgroup in whom the results of surgical resection were superior or comparable to those of transplantation. Tumor burden determination could be a useful tool for patient subclassification and help guide therapeutic decision-making.
PubMed: 38789311
DOI: 10.1016/j.rgmxen.2022.12.001