Over the past six decades, liver transplantation (LT) has evolved from an experimental procedure into a standardized and life-saving intervention, reshaping the landscape of organ transplantation. Driven by pioneering breakthroughs, technological advancements, and a deepened understanding of immunology, LT has seen remarkable progress. Some of the most notable breakthroughs in the field include advances in immunosuppression, a revised model for end-stage liver disease, and artificial intelligence (AI)-integrated imaging modalities serving diagnostic and therapeutic roles in LT, paired with ever-evolving technological advances. Additionally, the refinement of transplantation procedures, resulting in the introduction of alternative transplantation methods, such as living donor LT, split LT, and the use of marginal grafts, has addressed the challenge of organ shortage. Moreover, precision medicine, guiding personalized immunosuppressive strategies, has significantly improved patient and graft survival rates while addressing emergent issues, such as short-term complications and early allograft dysfunction, leading to a more refined strategy and enhanced post-operative recovery. Looking ahead, ongoing research explores regenerative medicine, diagnostic tools, and AI to optimize organ allocation and post-transplantation car. In summary, the past six decades have marked a transformative journey in LT with a commitment to advancing science, medicine, and patient-centered care, offering hope and extending life to individuals worldwide.

ZFYVE19-associated progressive familial intrahepatic cholestasis is a rare ciliopathy, with limited information on its natural history.

Investigate long-term outcomes, especially after liver transplantation (LT), in ZFYVE19-deficient patients.

Medical data of 13 Chinese individuals genetically diagnosed with ZFYVE19 deficiency, including 4 unreported patients, were reviewed.

All patients harbored biallelic null variants in ZFYVE19 and were alive at a median age of 13.2 years (range 1.1-39) with a median follow-up of 6.4 years (range 1-19.7). The first manifestation was neonatal cholestasis in 4 patients, isolated abnormal hepatobiliary-injury biomarkers in 3, and portal hypertension in 6. Eleven patients were administered ursodeoxycholic acid, with temporary normalization of hepatobiliary-injury biomarkers in 7. Six patients underwent LT (4 with living-related donors) at a median age of 3.5 years (range 0.6-7). After a median follow-up of 5.3 years (range 0.5-19) after LT, all 6 patients survived and were asymptomatic. Chronic renal disease or malignancy has not supervened.

ZFYVE19 deficiency caused by biallelic null variants primarily affects the liver without clinically significant involvement of other organs. ZFYVE19-related neonatal cholestasis can progress to liver failure necessitating LT in infancy. Ursodeoxycholic acid may improve hepatobiliary indices but may not avoid cirrhosis / LT. LT outcomes are generally good, even with parental grafts.

Imaging remains an essential aspect in evaluating patients receiving liver transplants, especially in cases of complications such as portal vein thrombosis. Several imaging modalities are available to approach portal vein thrombosis, with portography as the gold standard. However, the development of noninvasive methods such as contrast-enhanced computed tomography (CECT) is preferred nowadays due to the fewer complications in nature. This case report presented a case of a giant varix of the portal vein with thrombus in a 20-year-old male receiving living-donor liver transplant, reliably visualized in both CECT and direct splenoportography. Detailed parameters and sequences required for accurate imaging in CECT are discussed in this study.

Hepatic encephalopathy and other neurodegenerative disorders have profound implications for extensive liver impairment, calling for new ways of treating the condition. The application of stem cell transplantation to treat these severe disorders is a new and encouraging technique. This review article digs deep into the subject of stem cell transplantation therapy, neurodegenerative disorders associated with advanced liver damage, and liver transplantation. It comprehensively analyses the background, rationale, scope, and objectives of using stem cells to treat such challenging conditions. The topic of discussion includes the subtleties of neurodegenerative disorders, the function of liver transplantation, and the possible advantages and disadvantages associated with it. The relevance of patient selection, intraoperative concerns and post-transplant care is discussed. Further, the article explores how stem cell-based therapies can benefit from nanotechnology, specifically how it can improve stem cell distribution, survival, and integration for better therapeutic results. This review aims to offer a thorough analysis of regenerative medicine's present and future possibilities in dealing with the intricate relationship between neurodegeneration and liver damage. It does this by examining the efficacy, safety, and long-term impacts of stem cell transplantation in treating neurodegenerative disorders associated with advanced liver damage. This will incorporate insights from ongoing clinical trials, the patent landscape, and future directions. The goal is to pave the way for innovative and personalized treatment approaches in this evolving research and clinical practice field. Therefore, these efforts represent a promising frontier in medical research that can alleviate the burden of HE and associated neurological complications combined with liver cirrhosis.

Advancements in surgical techniques and the optimization of immunosuppression have boosted organ transplant survival rates; however, liver transplant recipients still risk complications such as hepatic vein occlusive disease (HVOD), also called sinusoidal obstruction syndrome. Rare but potentially fatal HVOD damages endothelial cells due to factors like chemotherapy, stem cell transplantation, and certain medications such as azathioprine and tacrolimus. Typically, HVOD presents with distinct clinical symptoms, including ascites, jaundice, and significant weight gain. Herein, we present the case of a 66-year-old male with decompensated liver cirrhosis due to hepatitis C virus infection. The patient underwent a deceased donor liver transplantation at our center. Unfortunately, 4 months after the transplant, he experienced progressive dyspnea and developed right pleural effusion. Abdominal computed tomography and a liver biopsy confirmed the diagnosis of HVOD, likely induced by tacrolimus. After stopping tacrolimus, we observed a significant decrease in ascites and remission of the patient's clinical symptoms of abdominal distention and dyspnea; subsequently, we introduced cyclosporine. In this report, we describe this specific patient's case and discuss HVOD, including its diagnosis and management.

Post-transplant complications reduce allograft and recipient survival. Current approaches for detecting allograft injury non-invasively are limited and do not differentiate between cellular mechanisms. Here, we monitor cellular damages after liver transplants from cell-free DNA (cfDNA) fragments released from dying cells into the circulation. We analyzed 130 blood samples collected from 44 patients at different time points after transplant. Sequence-based methylation of cfDNA fragments were mapped to patterns established to identify cell types in different organs. For liver cell types DNA methylation patterns and multi-omic data integration show distinct enrichment in open chromatin and regulatory regions functionally important for the respective cell types. We find that multi-tissue cellular damages post-transplant recover in patients without allograft injury during the first post-operative week. However, sustained elevation of hepatocyte and biliary epithelial cfDNA beyond the first week indicates early-onset allograft injury. Further, cfDNA composition differentiates amongst causes of allograft injury indicating the potential for non-invasive monitoring and timely intervention.

The use of marginal grafts is very challenging and is associated with post-reperfusion syndrome and early allograft dysfunction. The outcomes of machine perfusion for the preservation of marginal grafts have been compared with that of static cold storage, with studies reporting a reduced risk of ischemic cholangiopathy and graft loss. We performed this systematic review and meta-analysis of randomized controlled trials (RCTs) comparing outcomes of machine perfusion of liver grafts to static cold storage (SCS) of liver grafts during liver transplantation. Two independent researchers thoroughly searched for literature in the following databases: PubMed (Medline), Cochrane Central Register of Controlled Studies (CENTRAL), clinical trial registry, ResearchGate, Google Scholar, and Scopus (ELSEVIER) databases (last search: November 2023). The search terms used were: "dynamic perfusion," "normothermic perfusion," "hypothermic perfusion," "liver transplantation," "static cold storage," "NMP," "HOPE," "extended criteria grafts," "marginal grafts," "RCTs," "randomized controlled trials," "warm ischemia," and "cold ischemia." Eight RCTs published between 2019 and 2023 were included in the data synthesis and meta-analysis. The primary outcome considered was the overall incidence of early allograft dysfunction (EAD) between the two methods of graft perfusion after liver transplantation. The secondary outcome considered was the rate of retransplantation. Our meta-analysis revealed that SCS is associated with more EAD when compared with machine perfusion, with a p-value of <0.00001. We also found that the rate of retransplantation is higher among patients who received a liver preserved by SCS, with a p-value of 0.02. The use of machine perfusion in the preservation of liver grafts showed a significant reduction in early allograft dysfunction and retransplantation.

Evaluation of the effectiveness of CT-guided drainage (CTD) placement in managing symptomatic postoperative fluid collections in liver transplant patients. The assessment included technical success, clinical outcomes, and the occurrence of complications during the peri-interventional period.

Analysis spanned the years 2005 to 2020 and involved 91 drain placement sessions in 50 patients using percutaneous transabdominal or transhepatic access. Criteria for technical success (TS) included (a) achieving adequate drainage of the fluid collection and (b) the absence of peri-interventional complications necessitating minor or prolonged hospitalization. Clinical success (CS) was characterized by (a) a reduction or normalization of inflammatory blood parameters within 30 days after CTD placement and (b) the absence of a need for surgical revision within 60 days after the intervention. Inflammatory markers in terms of C-reactive protein (CRP), leukocyte count and interleukin-6, were evaluated. The dose length product (DLP) for various intervention steps was calculated.

The TS rate was 93.4%. CS rates were 64.3% for CRP, 77.8% for leukocytes, and 54.5% for interleukin-6. Median time until successful decrease was 5.0 days for CRP and 3.0 days for leukocytes and interleukin-6. Surgical revision was not necessary in 94.0% of the cases. During the second half of the observation period, there was a trend (p = 0.328) towards a lower DLP for the entire intervention procedure (median: years 2013 to 2020: 623.0 mGy·cm vs. years 2005 to 2012: 811.5 mGy·cm). DLP for the CT fluoroscopy component was significantly (p = 0.001) lower in the later period (median: years 2013 to 2020: 31.0 mGy·cm vs. years 2005 to 2012: 80.5 mGy·cm).

The TS rate of CT-guided drainage (CTD) placement was notably high. The CS rate ranged from fair to good. The reduction in radiation exposure over time can be attributed to advancements in CT technology and the growing expertise of interventional radiologists.