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Ultrasound in Medicine & Biology May 2024The World Federation for Ultrasound in Medicine and Biology (WFUMB) endorsed the development of this document on multiparametric ultrasound. Part 1 is an update to the... (Review)
Review
The World Federation for Ultrasound in Medicine and Biology (WFUMB) endorsed the development of this document on multiparametric ultrasound. Part 1 is an update to the WFUMB Liver Elastography Guidelines Update released in 2018 and provides new evidence on the role of ultrasound elastography in chronic liver disease. The recommendations in this update were made and graded using the Oxford classification, including level of evidence (LoE), grade of recommendation (GoR) and proportion of agreement (Oxford Centre for Evidence-Based Medicine [OCEBM] 2009). The guidelines are clinically oriented, and the role of shear wave elastography in both fibrosis staging and prognostication in different etiologies of liver disease is discussed, highlighting advantages and limitations. A comprehensive section is devoted to the assessment of portal hypertension, with specific recommendations for the interpretation of liver and spleen stiffness measurements in this setting.
PubMed: 38762390
DOI: 10.1016/j.ultrasmedbio.2024.03.013 -
Liver Cancer Apr 2024Lenvatinib is indicated for the forefront treatment of advanced hepatocellular carcinoma (aHCC), but its use may be limited by the risk of esophagogastric varices (EGV)...
INTRODUCTION
Lenvatinib is indicated for the forefront treatment of advanced hepatocellular carcinoma (aHCC), but its use may be limited by the risk of esophagogastric varices (EGV) bleeding. This study assessed the prevalence, predictors, and complications of EGV in aHCC patients treated with lenvatinib.
METHODS
In this multicenter international retrospective study, cirrhotic patients treated with lenvatinib for aHCC, were enrolled if upper-gastrointestinal endoscopy was available within 6 months before treatment. Primary endpoint was the incidence of EGV bleeding during lenvatinib therapy; secondary endpoints were predictors for EGV bleeding, prevalence, and risk factors for the presence of EGV and high-risk EGV at baseline, as well as impact of EGV bleeding on patients' survival.
RESULTS
535 patients were enrolled in the study (median age: 72 years, 78% male, 63% viral etiology, 89% Child-Pugh A, 16% neoplastic portal vein thrombosis [nPVT], 56% Barcelona Clinic Liver Cancer-C): 234 had EGV (44%), 70 (30%) were at high risk and 59 were on primary prophylaxis. During lenvatinib treatment, 17 patients bled from EGV (3 grade 5), the 12-month cumulative incidence being 3%. The only baseline independent predictor of EGV bleeding was the presence of baseline high-risk EGV (hazard ratio: 6.94, 95% confidence interval [CI]: 2.23-21.57, = 0.001). In these patients the 12-month risk was 17%. High-risk varices were independently associated with Child-Pugh B score (odds ratio [OR]: 2.12; 95% CI: 1.08-4.17, = 0.03), nPVT (OR: 2.54; 95% CI: 1.40-4.61, = 0.002), and platelets <150,000/μL (OR: 2.47; 95% CI: 1.35-4.50, = 0.003).
CONCLUSION
In hepatocellular carcinoma patients treated with lenvatinib, the risk of EGV bleeding was mostly low but significant only in patients with high-risk EGV at baseline.
PubMed: 38751557
DOI: 10.1159/000534127 -
Liver Cancer Apr 2024Cirrhosis is deemed to be a contributing factor to the postoperative recurrence of hepatocellular carcinoma (HCC); however, the precise impact of liver fibrosis on both...
INTRODUCTION
Cirrhosis is deemed to be a contributing factor to the postoperative recurrence of hepatocellular carcinoma (HCC); however, the precise impact of liver fibrosis on both cancer-specific prognoses remains unclear. This investigation sought to elucidate the effect of liver fibrosis severity on the cancer-specific prognosis.
METHODS
A total of 524 consecutive patients were included. Recurrence-free survival (RFS) and disease-specific survival (DSS) were compared according to fibrosis stage. Moreover, postoperative outcomes were subjected to analysis in cohorts of patients with F0 and F1-3, as well as in those with F1-3 and F4, who were carefully matched for background factors.
RESULTS
The 5-year RFS exhibited a significantly worse outcome in the F4 group compared to other stages of fibrosis: 5-year RFS - F0 (46.6%), F1-3 (33.1%), and F4 (23.5%), = 0.03 (F0 vs. F1-3) and < 0.01 (F1-3 vs. F4). Additionally, the 5-year DSS also presented a significantly worse prognosis in the F4 group: 5-year DSS - F0 (82.9%), F1-3 (73.6%), and F4 (57.4%), = 0.04 (F0 vs. F1-3) and < 0.01 (F1-3 vs. F4). In multivariate analysis, fibrosis 1, 2, 3, and 4 stage (compared with F0) (HR: 1.70, 1.81, 1.89, and 3.99, 95% confidence interval: 1.10-1.99, 1.39-2.22, 1.41-2.55, and 2.25-5.01, = 0.022, = 0.008, < 0.001, and < 0.001, respectively) was independent risk factor for RFS. After matched analysis, both RFS and DSS exhibited significantly worse prognoses in the presence of more advanced fibrosis. There was a significantly higher incidence of multiple recurrences in the F4 group than the F1-3 group, and a number of recurrences were observed both in the same hepatic segment as the resected side and in the contralateral lobe in F4 group.
DISCUSSION/CONCLUSION
The hazard and recurrence pattern of HCC signifies that the prognosis could potentially be poor, as the hepatic fibrosis likely owing to a higher hepatocarcinogenic potential, even in the absence of progression to cirrhotic condition. The risk of de novo recurrence may also increase with the progression of this fibrosis.
PubMed: 38751553
DOI: 10.1159/000533857 -
Journal of Translational Medicine May 2024Changes in plasma protein glycosylation are known to functionally affect proteins and to associate with liver diseases, including cirrhosis and hepatocellular carcinoma.... (Comparative Study)
Comparative Study
BACKGROUND
Changes in plasma protein glycosylation are known to functionally affect proteins and to associate with liver diseases, including cirrhosis and hepatocellular carcinoma. Autoimmune hepatitis (AIH) is a liver disease characterized by liver inflammation and raised serum levels of IgG, and is difficult to distinguish from other liver diseases. The aim of this study was to examine plasma and IgG-specific N-glycosylation in AIH and compare it with healthy controls and other liver diseases.
METHODS
In this cross-sectional cohort study, total plasma N-glycosylation and IgG Fc glycosylation analysis was performed by mass spectrometry for 66 AIH patients, 60 age- and sex-matched healthy controls, 31 primary biliary cholangitis patients, 10 primary sclerosing cholangitis patients, 30 non-alcoholic fatty liver disease patients and 74 patients with viral or alcoholic hepatitis. A total of 121 glycans were quantified per individual. Associations between glycosylation traits and AIH were investigated as compared to healthy controls and other liver diseases.
RESULTS
Glycan traits bisection (OR: 3.78 [1.88-9.35], p-value: 5.88 × 10), tetraantennary sialylation per galactose (A4GS) (OR: 2.88 [1.75-5.16], p-value: 1.63 × 10), IgG1 galactosylation (OR: 0.35 [0.2-0.58], p-value: 3.47 × 10) and hybrid type glycans (OR: 2.73 [1.67-4.89], p-value: 2.31 × 10) were found as discriminators between AIH and healthy controls. High A4GS differentiated AIH from other liver diseases, while bisection associated with cirrhosis severity.
CONCLUSIONS
Compared to other liver diseases, AIH shows distinctively high A4GS levels in plasma, with potential implications on glycoprotein function and clearance. Plasma-derived glycosylation has potential to be used as a diagnostic marker for AIH in the future. This may alleviate the need for a liver biopsy at diagnosis. Glycosidic changes should be investigated further in longitudinal studies and may be used for diagnostic and monitoring purposes in the future.
Topics: Humans; Hepatitis, Autoimmune; Female; Male; Polysaccharides; Middle Aged; Glycosylation; Case-Control Studies; Immunoglobulin G; Liver Diseases; Adult; Cross-Sectional Studies; Aged
PubMed: 38745252
DOI: 10.1186/s12967-024-05173-z -
Experimental and Clinical... Apr 2024Mucormycosis, a group of opportunistic mycoses caused by Mucorales, present a significant threat to immunocompromised patients. In this report, we present the case of a...
Mucormycosis, a group of opportunistic mycoses caused by Mucorales, present a significant threat to immunocompromised patients. In this report, we present the case of a 57-year-old male patient who underwent liver transplant for secondary biliary cirrhosis following inadvertent bile duct injury. Despite initial satisfactory postoperative evolution, the patient developed fever, and imaging revealed a suspicious lesion. Preliminary culture growth suggested a filamentous fungus, leading to initiation of liposomal amphotericin B. However, the lesion progressed, and a surgical debridement was necessary. During surgery, involvement of the liver dome and diaphragm was observed, and a nonanatomical hepatectomy was performed. Despite efforts, the patient's condition deteriorated, ultimately resulting in multiple organ failure and mortality. This case emphasizes the challenging nature of mucormycosis in livertransplant recipients.
Topics: Humans; Male; Mucormycosis; Middle Aged; Liver Transplantation; Antifungal Agents; Immunocompromised Host; Fatal Outcome; Liver Cirrhosis, Biliary; Treatment Outcome; Opportunistic Infections; Debridement; Allografts; Hepatectomy; Amphotericin B; Multiple Organ Failure
PubMed: 38742324
DOI: 10.6002/ect.2023.0142 -
Clinical and Translational Medicine May 2024Early diagnosis of hepatocellular carcinoma (HCC) can significantly improve patient survival. We aimed to develop a blood-based assay to aid in the diagnosis, detection...
BACKGROUND
Early diagnosis of hepatocellular carcinoma (HCC) can significantly improve patient survival. We aimed to develop a blood-based assay to aid in the diagnosis, detection and prognostic evaluation of HCC.
METHODS
A three-phase multicentre study was conducted to screen, optimise and validate HCC-specific differentially methylated regions (DMRs) using next-generation sequencing and quantitative methylation-specific PCR (qMSP).
RESULTS
Genome-wide methylation profiling was conducted to identify DMRs distinguishing HCC tumours from peritumoural tissues and healthy plasmas. The twenty most effective DMRs were verified and incorporated into a multilocus qMSP assay (HepaAiQ). The HepaAiQ model was trained to separate 293 HCC patients (Barcelona Clinic Liver Cancer (BCLC) stage 0/A, 224) from 266 controls including chronic hepatitis B (CHB) or liver cirrhosis (LC) (CHB/LC, 96), benign hepatic lesions (BHL, 23), and healthy controls (HC, 147). The model achieved an area under the curve (AUC) of 0.944 with a sensitivity of 86.0% in HCC and a specificity of 92.1% in controls. Blind validation of the HepaAiQ model in a cohort of 523 participants resulted in an AUC of 0.940 with a sensitivity of 84.4% in 205 HCC cases (BCLC stage 0/A, 167) and a specificity of 90.3% in 318 controls (CHB/LC, 100; BHL, 102; HC, 116). When evaluated in an independent test set, the HepaAiQ model exhibited a sensitivity of 70.8% in 65 HCC patients at BCLC stage 0/A and a specificity of 89.5% in 124 patients with CHB/LC. Moreover, HepaAiQ model was assessed in paired pre- and postoperative plasma samples from 103 HCC patients and correlated with 2-year patient outcomes. Patients with high postoperative HepaAiQ score showed a higher recurrence risk (Hazard ratio, 3.33, p < .001).
CONCLUSIONS
HepaAiQ, a noninvasive qMSP assay, was developed to accurately measure HCC-specific DMRs and shows great potential for the diagnosis, detection and prognosis of HCC, benefiting at-risk populations.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Female; Male; DNA Methylation; Middle Aged; Prognosis; Early Detection of Cancer; Circulating Tumor DNA; Cohort Studies; Biomarkers, Tumor; Aged; Adult
PubMed: 38741204
DOI: 10.1002/ctm2.1652 -
Case Reports in Gastroenterology 2024Secondary sclerosing cholangitis in critically ill patients (SSC-CIP) is a rare but underdiagnosed entity that occurs after life-threatening events and treatment in the...
INTRODUCTION
Secondary sclerosing cholangitis in critically ill patients (SSC-CIP) is a rare but underdiagnosed entity that occurs after life-threatening events and treatment in the intensive care unit (ICU). The etiology of SSC-CIP is not fully understood but may be caused by ischemic bile duct injury. SSC-CIP is a cholestatic liver disease that rapidly progresses to liver cirrhosis, with a high mortality rate in the first year of 50%. Endoscopic retrograde cholangiopancreatography (ERCP), which is the gold standard for diagnosing SSC-CIP, shows primary SC-like changes, usually in the intrahepatic bile ducts. Biliary cast formation is pathognomonic for SSC-CIP. No proven effective conservative treatment is available for SSC-CIP, and liver transplantation is the only curative therapy when liver cirrhosis or recurrent cholangitis occurs.
CASE PRESENTATION
We report the case of a 47-year-old male patient who developed cholestasis after a long treatment in the ICU for severe pneumonia. ERCP showed characteristic findings with rarefication and multiple segmental stenosis in the intrahepatic bile ducts. We removed multiple biliary casts from the bile ducts.
CONCLUSION
SSC-CIP should be considered for ICU patients with unclear cholestasis, especially when the cholestasis persists after recovery from the underlying disease. Early diagnosis is important to achieve better outcomes; without liver transplantation, the prognosis is generally poor.
PubMed: 38737441
DOI: 10.1159/000537957 -
United European Gastroenterology Journal May 2024The impact of dominant stricture (DS) on the outcomes of paediatric-onset primary sclerosing cholangitis (PSC) is unknown. This study was aimed at investigating the...
BACKGROUND AND OBJECTIVES
The impact of dominant stricture (DS) on the outcomes of paediatric-onset primary sclerosing cholangitis (PSC) is unknown. This study was aimed at investigating the impact of DS on the clinical course and prognosis of patients with paediatric-onset PSC.
METHODS
Patients with paediatric-onset PSC diagnosed between January 1993 and May 2017 were identified from hospital records or our PSC registry. Data including clinical, laboratory, cholangiography, and cytology at diagnosis and during follow-up (until July 2023) were reviewed. We graphed the Kaplan-Meier failure function and fitted crude and multivariable Cox model to calculate hazard ratios (HR) and 95% confidence intervals (CI) for selected variables. In these analyses, DS was treated as a time-varying variable.
RESULTS
We identified 68 patients (42 males) with paediatric-onset PSC (median age at diagnosis 15 years). The median follow-up was 13 years and the median age at the last follow-up was 27 years. In total, 35 (51%) had concomitant autoimmune hepatitis. DS was diagnosed in 33 patients (48%): in eight at the time of PSC diagnosis (12%) and in 25 (37%) by the end of follow-up. In patients with DS, two developed cirrhosis, seven were transplanted and one patient was operated for a biliary mass with low-grade dysplasia. In patients without a DS, two developed cirrhosis, and four were transplanted; one female was excluded from survival analysis because she already had cirrhosis at the time of PSC diagnosis. Cirrhosis or biliary dysplasia or needing liver transplantation for these indications were more frequent after the development of DS (10/33, adjusted HR 4.26, 95%CI: 1.26-14.4). No cholangiocarcinomas or deaths occurred during the follow-up.
CONCLUSIONS
DS was present at diagnosis or developed during follow-up in about half of the patients with paediatric-onset PSC and was associated with impaired outcome.
PubMed: 38733616
DOI: 10.1002/ueg2.12583 -
Journal of Clinical Medicine May 2024Acute cholecystitis (AC), generally associated with the presence of gallstones, is a relatively frequent disease that can lead to serious complications. For these... (Review)
Review
Acute cholecystitis (AC), generally associated with the presence of gallstones, is a relatively frequent disease that can lead to serious complications. For these reasons, AC warrants prompt clinical diagnosis and management. There is general agreement in terms of considering early laparoscopic cholecystectomy (ELC) to be the best treatment for AC. The optimal timeframe to perform ELC is within 72 h from diagnosis, with a possible extension of up to 7-10 days from symptom onset. In the first hours or days after hospital admission, before an ELC procedure, the patient's medical management comprises fasting, intravenous fluid infusion, antimicrobial therapy, and possible administration of analgesics. Additionally, concomitant conditions such as choledocholithiasis, cholangitis, biliary pancreatitis, or systemic complications must be recognized and adequately treated. The importance of ELC is related to the frequent recurrence of symptoms and complications of gallstone disease in the interval period between the onset of AC and surgical intervention. In patients who are not eligible for ELC, it is suggested to delay surgery at least 6 weeks after the clinical presentation. Critically ill patients, who are unfit for surgery, may require rescue treatments, such as percutaneous or endoscopic gallbladder drainage (GBD). A particular treatment approach should be applied to special populations such as pregnant women, cirrhotic, and elderly patients. In this review, we provide a practical diagnostic and therapeutic approach to AC, even in specific clinical situations, based on evidence from the literature.
PubMed: 38731224
DOI: 10.3390/jcm13092695 -
Transplantation Proceedings May 2024There is continuous growth of combined liver-kidney transplantation (CLKTx) numbers with remarkable outcomes, especially among patient with liver cirrhosis and end-stage...
BACKGROUND
There is continuous growth of combined liver-kidney transplantation (CLKTx) numbers with remarkable outcomes, especially among patient with liver cirrhosis and end-stage renal disease. The aim was to present a single center experience.
METHODS
Twenty patients (9 males) with a mean age of 48 (range: 20-62) years underwent CLKTx from 2005 to 2022. Indications were polycystic liver and kidney diseases (ADPKD) in 12 cases, cirrhosis due to hepatitis (4 patients), and 1 case of amyloidosis, alcoholic liver disease, nonalcoholic steatosis, and congenital hepatic fibrosis with concomitant glomerulonephritis. After hepatectomy, half of the patients had orthotopic liver transplantation with piggy-back technique, and the other had conventional technique. All but 1 recipient had biliary end-to-end anastomosis. 3 patients had preemptive kidney graft transplantation. 4 underwent simultaneous right-side nephrectomy due to volume of the right kidney. Kidney was transplanted from the separate incision after abdominal closure with typical anastomoses. Tacrolimus, mycophenolate mofetile, basiliximab, and steroids were applied for all recipients.
RESULTS
Mean follow-up was 57.7 ± 54 months. No primary non-function of the grafts occurred. Delayed kidney graft function (DGF) occurred in 8 patients. Three-month, 1-year, and 5-year cumulative survival rates were: 90%, 80%, and 72% respectively. None of the patients required retransplantation, and 1 recipient returned to hemodialysis 19 months after transplantation. Preemptive kidney transplantation and simultaneous right-side nephrectomy were not significant for DGF and recipient survival. No deaths within the first year occurred in piggy-back technique.
CONCLUSIONS
CLKTx is safe and effective in the treatment of both liver and kidney failure.
PubMed: 38719623
DOI: 10.1016/j.transproceed.2024.03.014