Prospective study of hepatitis B and D epidemiology and risk factors in Romania: A 10-year update.

BACKGROUND: The global burden of hepatitis D virus (HDV) infection represents a major medical challenge and a public health crisis worldwide. However, there is a lack of accurate data on the epidemiology and risk factors for HDV. Hepatitis B virus (HBV) and HDV coinfection causes the most severe form of viral hepatitis, leading to a higher cumulative incidence of liver-related events compared with HBV monoinfection, including the need for liver transplantation and death. AIM: To investigate the epidemiology, natural history, risk factors and clinical management of HBV and HDV coinfection in Romanian patients. METHODS: This prospective study was conducted between January and July 2022 in six tertiary gastroenterology and hepatology referral centres in Romania. All consecutive adults admitted for any gastroenterology diagnosis who were HBV-positive were enrolled. Patients with acute hepatitis or incomplete data were excluded. Of the 25390 individuals who presented with any type of gastroenterology diagnosis during the study period, 963 met the inclusion criteria. Testing for anti-HDV antibodies and HDV RNA was performed for all participants. Demographic and risk factor data were collected by investigators using medical charts and patient questionnaires. All data were stored in an anonymized online database during the study. RESULTS: The prevalence of HBV was 3.8%; among these patients, the prevalence of HBV/HDV coinfection was 33.1%. The median age of the study population was 54.0 years, and it consisted of 55.1% men. A higher prevalence of HBV/HDV coinfection was observed in patients 50-69 years old. Patients with HBV/HDV coinfection were significantly older than those with HBV monoinfection (P = 0.03). Multivariate multiple regression analysis identified female gender (P = 0.0006), imprisonment (P < 0.0001), older age at diagnosis (P = 0.01) and sexual contact with persons with known viral hepatitis (P = 0.0003) as significant risk factors for HDV. CONCLUSION: This study shows that HDV infection among those with HBV remains endemic in Romania and updates our understanding of HDV epidemiology and associated risk factors. It emphasizes the need for systematic screening for HDV infection and collaborative initiatives for controlling and preventing HBV and HDV infection.

Quality of life in sarcopenia measured with the SarQoL questionnaire: A meta-analysis of individual patient data.

Age-related sarcopenia, resulting from a gradual loss in skeletal muscle mass and strength, is pivotal to the increased prevalence of functional limitation among the older adult community. The purpose of this meta-analysis of individual patient data is to investigate the difference in health-related quality of life between sarcopenic individuals and those without the condition using the Sarcopenia Quality of Life (SarQoL) questionnaire. A protocol was published on PROSPERO. Multiple databases and the grey literature were searched until March 2023 for studies reporting quality of life assessed with the SarQoL for patients with and without sarcopenia. Two researchers conducted the systematic review independently. A two-stage meta-analysis was performed. First, crude (mean difference) and adjusted (beta coefficient) effect sizes were calculated within each database; then, a random effect meta-analysis was applied to pool them. Heterogeneity was measured using the Q-test and I2 value. Subgroup analyses were performed to investigate the source of potential heterogeneity. The strength of evidence of this association was assessed using GRADE. From the 413 studies identified, 32 were eventually included, of which 10 were unpublished data studies. Sarcopenic participants displayed significantly reduced health-related quality of life compared with non-sarcopenic individuals (mean difference = -12.32; 95 % CI = [-15.27; -9.37]). The model revealed significant heterogeneity. Subgroup analyses revealed a substantial impact of regions, clinical settings, and diagnostic criteria on the difference in health-related quality of life between sarcopenic and non-sarcopenic individuals. The level of evidence was moderate. This meta-analysis of individual patient data suggested that sarcopenia is associated with lower health-related quality of life measured with SarQoL.

Improving primary prophylaxis of variceal bleeding by adapting therapy to the clinical stage of cirrhosis. A competing-risk meta-analysis of individual participant data.

BACKGROUND & AIMS: Non-selective ß-blockers (NSBBs) and endoscopic variceal-ligation (EVL) have similar efficacy preventing first variceal bleeding. Compensated and decompensated cirrhosis are markedly different stages, which may impact treatment outcomes. We aimed to assess the efficacy of NSBBs vs EVL on survival in patients with high-risk varices without previous bleeding, stratifying risk according to compensated/decompensated stage of cirrhosis. METHODS: By systematic review, we identified RCTs comparing NSBBs vs EVL, in monotherapy or combined, for primary bleeding prevention. We performed a competing-risk, time-to-event meta-analysis, using individual patient data (IPD) obtained from principal investigators of RCTs. Analyses were stratified according to previous decompensation of cirrhosis. RESULTS: Of 25 RCTs eligible, 14 failed to provide IPD and 11 were included, comprising 1400 patients (656 compensated, 744 decompensated), treated with NSBBs (N = 625), EVL (N = 546) or NSBB+EVL (N = 229). Baseline characteristics were similar between groups. Overall, mortality risk was similar with EVL vs. NSBBs (subdistribution hazard-ratio (sHR) = 1.05, 95% CI = 0.75-1.49) and with EVL + NSBBs vs either monotherapy, with low heterogeneity (I2 = 28.7%). In compensated patients, mortality risk was higher with EVL vs NSBBs (sHR = 1.76, 95% CI = 1.11-2.77) and not significantly lower with NSBBs+EVL vs NSBBs, without heterogeneity (I2 = 0%). In decompensated patients, mortality risk was similar with EVL vs. NSBBs and with NSBBs+EVL vs. either monotherapy. CONCLUSIONS: In patients with compensated cirrhosis and high-risk varices on primary prophylaxis, NSBBs significantly improved survival vs EVL, with no additional benefit noted adding EVL to NSBBs. In decompensated patients, survival was similar with both therapies. The study suggests that NSBBs are preferable when advising preventive therapy in compensated patients.

Liquid biopsy for early detection of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a highly prevalent and lethal cancer globally. Over 90% of HCC cases arise in the context of liver cirrhosis, and the severity of the underlying liver disease or advanced tumor stage at diagnosis significantly limits treatment options. Early diagnosis is crucial, and all guidelines stress the importance of screening protocols for HCC early detection as a public health objective. As serum biomarkers are not optimal for early diagnosis, liquid biopsy has emerged as a promising tool for diagnosis, prognostication, and patients' stratification for personalized therapy in various solid tumors, including HCC. While circulating tumor cells (CTCs) are better suited for personalized therapy and prognosis, cell-free DNA (cfDNA) and extracellular vesicle-based technologies show potential for early diagnosis, HCC screening, and surveillance protocols. Evaluating the added value of liquid biopsy genetic and epigenetic biomarkers for HCC screening is a key goal in translational research. Somatic mutations commonly found in HCC can be investigated in cfDNA and plasma exosomes as genetic biomarkers. Unique methylation patterns in cfDNA or cfDNA fragmentome features have been suggested as innovative tools for early HCC detection. Likewise, extracellular vesicle cargo biomarkers such as miRNAs and long non-coding RNAs may serve as potential biomarkers for early HCC detection. This review will explore recent findings on the utility of liquid biopsy for early HCC diagnosis. Combining liquid biopsy methods with traditional serological biomarkers could improve the overall diagnostic accuracy for early HCC detection.

Real-Life Results of Palliative Chemotherapy in Metastatic Pancreatic Ductal Adenocarcinoma.

PURPOSE: To assess the efficacy of FOLFIRINOX(FFX), gemcitabine-based regimens (GB), and gemcitabine monotherapy (Gem) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). METHODS: This is a retrospective study that included 83 patients with mPDAC treated with first-line chemotherapy (L1) with either FFX, GB or Gem between 2015 and 2017. Progression-free survival (PFS) for L1 and second-line chemotherapy (L2) (PFS-L1 and PFS-L2) and overall survival (OS) were estimated using the Kaplan-Meier method. RESULTS: Median PFS-L1 for FFX, GB and Gem groups was 9 months (95% (Confidence Interval) CI 2.76-15.24), 5 months (95%CI 3.44-6.56), and 5 months (95%CI 3.76-6.24), respectively (p = 0.04). OS was 14 months (95%CI 11.16-16.85), 12 months (95%CI: 9.44-11.56), and 7 months (95%CI: 5.7-8.3) for patients treated with FFX, GB, and Gem, respectively (p = 0.0001). ECOG-PS (0/1) (Hazard Ratio (HR) 6.74, p = 0.002), age > 70 years (HR 0.25, p = 0.04), body tumors (HR 2.8, p = 0.048), CA19-9 > 39 U/mL (HR 0.26, p = 0.02), and neutrophil-to-lymphocyte ratio (NLR) > 4.15 (HR 6.76, p = 0.001) were independent prognostic factors for PFS-L1. Male gender (HR 3.02, p = 0.026), ECOG-PS (0/1) (HR 4.21, p = 0.003), L1 with FFX (HR 0.255, p = 0.007), and NLR > 4.15 (HR 2.65, p = 0.04) were independent prognostic factors of OS. PFS-L2 (HR 6.91, p = 0.013) and OS-L2 (HR 6.95, p = 0.037) were significantly higher in patients first treated with FFX. CONCLUSIONS: The OS of patients who receive FFX or GB is comparable. The best PFS-L1 belongs to the FFX group. Male gender, ECOG-PS 0/1, the FFX regimen, and NLR > 4.15 were independent predictors of OS. PFS-L2 and OS-L2 were favorably impacted by L1 with FFX.

Real World Efficacy and Safety of Sofosbuvir + Velpatasvir + Voxilaprevir in Romanian Patients with Genotype 1b HCV Infection Non-reponders to DAAs Therapy.

BACKGROUND AND AIMS: The sofosbuvir (SOF) / velpatasvir (VEL) / voxilaprevir (VOX) combination has been evaluated in more than 800 patients enrolled in phase II and phase III studies, where it demonstrated excellent safety and efficacy, achieving overall sustained viral response (SVR) rates of more than 95%. We aimed to assess the efficacy and safety of SOF/VEL/VOX in a real-world study, including patients previously treated for genotype 1b hepatitis C virus (HCV) infection that did not obtain a sustained viral response with previous direct-acting antivirals (DAAs) therapy. METHODS: In Romania, through a nationwide government-funded program in 2019-2020, 213 patients with chronic hepatitis C non-responders to previous DAAs therapy, received treatment with SOF/VEL/ VOX 400/100/100 mg/day for 12 weeks. We performed a retrospective longitudinal study that included 143 individuals who were treated in Bucharest, Iași, Craiova and Constanța clinics, all with genotype 1b HCV infection. Efficacy was assessed by the percentage of patients achieving SVR 12 weeks post-treatment (SVR12). Serious adverse events (SAE) were registered. RESULTS: Our cohort comprised 53% males with a median age of 60 years (27÷77); 47% were pre-treated with ombitasvir/paritaprevir/ritonavir+dasabuvir ± ribavirin, 40% with ledipasvir/SOF, 13% with elbasvir/ grazoprevir. 42% of patients associated co-morbidities, 45% had compensated liver cirrhosis, 2% had treated hepatocellular carcinoma (HCC) and 1% had hepatitis B virus co-infection. SVR by intention to treat was reported in 139/143 (97.2%) and per protocol in 141/143 (98.6%). No predictive factors for SVR were identified. Rate of liver decompensation in patients with cirrhosis was 6% and was statistically associated in multivariate analysis with Child-Pugh score (p<0.01) and with severe steatosis (p=0.004). Occurrence of new HCC was reported in 3.6% of all patients with cirrhosis and was associated with poor liver function [higher Child-Pugh score (p=0.001) and low albumin levels (p=0.02)]. Serious adverse events related to therapy were reported in 1/143(0.7%). CONCLUSIONS: SOF/VEL/VOX was highly efficient in our population of patients with a 97.2% SVR. Liver decompensation occurred in 6% of cirrhotic patients at SVR, related to hepatic dysfunction.

Host and immunosuppression-related factors influencing fibrosis occurrence post liver transplantation.

Post liver transplantation (LT) fibrosis has a negative impact on graft function. Cytokine production in the host immune response after LT may contribute to the variable CYP3A-dependent immunosuppressive drug disposition, with subsequent impact on liver fibrogenesis, together with host-related factors. We aimed to investigate whether the cytochrome P4503A5*3 (CYP3A5*3) or TBX21 genotypes impact post-LT liver fibrogenesis. Furthermore, the impact of immunosuppressants on cellular apoptosis has been evaluated using human hepatocytes harvested from cirrhotic explanted livers. We have enrolled 98 LT recipients that were followed for occurrence of liver fibrosis for at least 12 months. There was a statistically significant higher trough level of TAC in patients with homozygous CC-TBX21 genotype (7.83 ± 2.84 ng/ml) vs. 5.66 ± 2.16 ng/ml in patients without this genotype (p = 0.009). The following variables were identified as risk factors for fibrosis ≥2: donor age (p = 0.02), neutrophil to lymphocyte ratio (p = 0.04) and TBX21 genotype CC (p = 0.009). In the cell culture model cytometry analysis has indicated the lowest apoptotic cells percentage in human cirrhotic hepatocytes cultures treated with mycophenolate mofetil (MMF) (5%) and TAC + MMF (2%) whereas the highest apoptosis percentage was registered for the TAC alone (11%). The gene expression results are concordant to cytometry study results, indicating the lowest apoptotic effect for MMF and MMF + TAC immunosuppressive regimens. The allele 1993C of the SNP rs4794067 may predispose to the development of late significant fibrosis of the liver graft. MMF-based regimens have a favourable anti-apoptotic profile in vitro, supporting its use in case of LT recipients at high risk for liver graft fibrosis.

Cholangiocellular carcinoma occurrence after HCV eradication therapy: case series and review of the literature.

Hepatitis C viral (HCV) treatment has rapidly advanced with the use of direct-acting antivirals (DAA), and many patients achieve sustained virological response (SVR). Although the risk of liver tumors is greatly reduced, there are still patients who achieve SVR but will progress to hepatocellular carcinoma (HCC). HCV infection is also a known risk for cholangiocellular carcinoma (CLC), although it is considered a relative infrequent liver malignancy. We report a series of five cases of CLC in patients that achieved SVR after HCV treatment with DAA. There were three women and two males with a median age of 62 years (range 49 to 77 years). Four patients had liver cirrhosis at the time of their HCV treatment. The interval from achieving SVR until CLC diagnosis varied, ranging from 4 to 36 months (median=12). Three patients presented with advanced disease and had extrahepatic spread at the time of their diagnosis. One patient had a resectable tumor, with no recurrence 4 years later. In one case, the tumor was initially considered an atypical HCC and was treated by radiofrequency ablation. Three years later, she was diagnosed with a large tumor recurrence that was demonstrated to be a CLC on liver biopsy. The last two patients were older males with HCV compensated cirrhosis diagnosed with CLC more than two years after achieving SVR. Palliative chemotherapy was started in both. Only a handful of CLC cases have been reported in HCV patients after SVR. Clinicians should take into account the possible development of an aggressive CLC.

Liquid Biopsy in Squamous Cell Carcinoma of the Esophagus and of the Head and Neck.

Squamous cell carcinomas of the esophagus (ESCC) and of the head and neck (HNSCC) are two neoplasms that share common risk factors and have the same embryological origin, but a very different prognosis, the 5-year survival of HNSCC being almost double (40-50%) compared to the 5-year survival of ESCC (20%). Current guidelines emphasize the importance of screening for ESCC in patients diagnosed with head and neck cancers. A liquid biopsy is a novel tool for diagnosis, prognostic stratification, and personalized therapy. Liquid biopsy biomarkers for these two malignancies could help both their early detection, facilitate residual disease identification, and provide prognosis information. The present systematic review of the literature was aimed at describing the liquid biopsy biomarkers present in these two malignancies, with an emphasis on potential clinical applications.

Assessment of Sarcopenia Related Quality of Life Using SarQoL® Questionnaire in Patients With Liver Cirrhosis.

Introduction: Sarcopenia, malnutrition, physical deconditioning, and frailty contribute to a significantly altered quality of life (QoL) in patients with cirrhosis and sarcopenia. Aim: To investigate the sarcopenia-linked alterations of QoL by SarQoL® questionnaire in patients with end-stage liver disease. Methods: Consecutive patients with liver cirrhosis, admitted to our department between May and August 2021, completed the SarQoL® questionnaire by themselves. They were evaluated for sarcopenia according to the 2019 European Working Group on Sarcopenia in Older People (EWGSOP) definition [hand grip cut-offs and skeletal muscle index (SMI) calculation at CT scan]. Results: A total of 71 patients with liver cirrhosis were included in the study, with a median age of 54 years. Sarcopenia was present in 31.2% of patients with Child-Pugh class A, in 58.3% with class B, and in 93.5% with class C. The SarQoL® score was statistically significant and lower in Child-Pugh class C vs. class B and class A (70.2 vs. 66.5 vs. 52.5 points, p = 0.0002). The SarQoL® score was evaluated according to different complications of cirrhosis, with statistically significant lower scores in patients with sarcopenia (p < 0.0001), in patients with ascites requiring paracentesis (p = 0.0006), and in patients with hepatic encephalopathy (p < 0.0001). A cut-off level of 75.9 points for SarQoL® score can accurately detect sarcopenia in patients with end-stage liver disease [area under the receiver operating characteristic (AUROC) curve of.823, SE of 92.1%, SP of 45.5%, positive predictive value (PPV) and negative predictive value (NPV) of 66 and 83.3%, respectively, correctly classified 73.2% of cirrhotic patients with sarcopenia]. Conclusions: The use of SarQoL® questionnaire in cirrhotic patients can, at the same time, evaluate the quality of life and identify subjects with sarcopenia and altered QoL.

Bowel Ultrasound: a Non-invasive, Easy to Use Method to Predict the Need to Intensify Therapy in Inflammatory Bowel Disease Patients.

BACKGROUND AND AIMS: Bowel ultrasound (BU) is a non-invasive, inexpensive, widely available tool, valuable for inflammatory bowel disease (IBD) assessment. The aim of the present study was to investigate the clinical utility of BU to predict the need to intensify therapy in IBD patients. METHODS: One hundred seventeen IBD patients (89 Crohn's disease, and 28 ulcerative colitis) diagnosis established at least 6 months before enrolment, undergoing maintenance therapy were prospectively included in the study. Bowel ultrasound investigated the following parameters: the bowel wall thickness (BWT), loss of wall stratification, the presence of the bowel wall Doppler signal, the visible lymph nodes, the mucosal hyperechoic spots, and the irregular external bowel wall. The patients were followed-up for 6 months, registering the need to escalate the treatment regimen. Subgroup analyses were conducted for patients requiring immediate treatment intensification (37 subjects), due to active disease at baseline and patients with subsequent treatment intensification, in the 6 months follow-up period (21 cases) in comparison to patients that required no therapeutic optimization (59). RESULTS: During the follow-up, 49.6% of patients needed treatment escalation. All the investigated BU variables were significantly associated with the main outcome. In the multivariate analysis, the mean BWT (p<0.0001), and the presence of the bowel wall Doppler signal (p=0.007) were independent predictors of the main outcome. For the subgroup analyses: mean BWT (p=0.0001) and the presence of the bowel wall Doppler signal (p=0.01) were independent predictors for immediate treatment intensification (active disease at baseline) and mean BWT (p=0.0003) and the lack of bowel wall stratification (p=0.05) were independent predictors for the need of subsequent therapeutic optimization. Logistic regression prediction models and prediction scores (BU score) had the best AUROC values (>0.91) when compared to traditional biomarkers of active inflammation, such as C reactive protein or fecal calprotectin. CONCLUSION: Bowel ultrasound could be used as a non-invasive, easy to use diagnostic tool to predict the need to intensify therapy in patients with IBD.

Anticoagulation Therapy for Portal Vein Thrombosis in Patients with Cirrhosis in a Tertiary Center Experience.

BACKGROUND AND AIMS: The evidence regarding the use of anticoagulant (AC) agents in portal vein thrombosis (PVT) is increasing and, most patients undergo chronic treatment with low molecular weight heparin (LMWH) or vitamin K antagonists (VKA). Nevertheless, there are no clear data about who should receive antithrombotic therapy, when to initiate it, how long and what dose should be used for this set of patients. The aim of the study was to assess the outcome of patients with cirrhosis and portal vein thrombosis who received AC therapy, in terms of thrombus regression, bleeding events and survival rates. METHODS: This observational and retrospective study included 107 cirrhotic patients diagnosed with PVT in a single tertiary center between 2010-2019. 54 received low molecular weight heparin or vitamin K antagonist (AC treatment group) and 53 were untreated. All patients were periodically follow-up to assess the evolution of PVT (regression, progression, stable thrombus) and potential occurrence of bleeding events. RESULTS: The regression of portal vein thrombosis was significantly higher in the AC treatment group (OR=2.430; 95% CI=1.11-6.167; p=0.026), more than 50% of on-treatment patients experiencing regression of the thrombus. However, bleeding events were significantly more frequent in the AC treatment group (18.5% vs. 7.5%) and the risk of bleeding was associated with thrombocytes less than 50x103/mm3 (OR=8.266; 95%CI: 2.310-39.211; p=0.002). Survival was better in the AC treatment group (68.4% vs 48.7% at 5 years and 92.7% vs 77.8% at 1 year, p=0.038) and was lower in patients that experienced bleeding events (37.22% survival at 5 years, mean time survival 44 months, p=0.008). CONCLUSIONS: In our cohort of cirrhotic patients with PVT more than 50% of patients receiving AC therapy presented regression of the thrombus; most of them obtained partial recanalization. The bleeding complication rate was higher than expected, reaching 18%. The overall mortality was lower in the treated group.

Prediction of late allograft dysfunction following liver transplantation by immunological blood biomarkers.

BACKGROUND: An accelerated course of hepatic fibrosis may occur in liver transplantation (LT) patients despite normal or slightly abnormal liver blood tests. AIM: To identify screening tools based on blood biomarkers to predict late allograft dysfunction in LT recipients. METHODS: 174 LT recipients were enrolled. Liver biopsy, liver functional tests, cytokine quantitation in serum, as well as soluble MHC class I polypeptide-related sequence A and B (sMICA/sMICB) and soluble UL16 binding protein 2 (sULBP2) were performed. RESULTS: Patients with late graft dysfunction had a significantly higher donor age, lower albumin level, higher alanine (ALT) and aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), total bilirubin and alkaline phosphatase (ALP), higher sMICA, sULBP2, higher interleukin (IL) 6, interferon γ and lower IL10 in serum as compared to recipients without allograft dysfunction. In order to provide a better statistical accuracy for discriminating 5-year allograft dysfunction from other less progressive subtype of allograft injury, we established a predictive model, based on 7 parameters (serum ALP, ALT, AST, GGT, sMICA, IL6 and albumin) which provided an Area Under the Receiver Operating Characteristics (AUROC) curve of 0.905. CONCLUSIONS: Blood-based biomarkers can significantly improve prediction of late liver allograft outcome in LT patients. The new developed score comprising serum parameters, with an excellent AUROC, can be reliably used for diagnosing late allograft dysfunction in transplanted patients.

COVID-19 in liver transplant candidates: pretransplant and post-transplant outcomes - an ELITA/ELTR multicentre cohort study.

OBJECTIVE: Explore the impact of COVID-19 on patients on the waiting list for liver transplantation (LT) and on their post-LT course. DESIGN: Data from consecutive adult LT candidates with COVID-19 were collected across Europe in a dedicated registry and were analysed. RESULTS: From 21 February to 20 November 2020, 136 adult cases with laboratory-confirmed SARS-CoV-2 infection from 33 centres in 11 European countries were collected, with 113 having COVID-19. Thirty-seven (37/113, 32.7%) patients died after a median of 18 (10-30) days, with respiratory failure being the major cause (33/37, 89.2%). The 60-day mortality risk did not significantly change between first (35.3%, 95% CI 23.9% to 50.0%) and second (26.0%, 95% CI 16.2% to 40.2%) waves. Multivariable Cox regression analysis showed Laboratory Model for End-stage Liver Disease (Lab-MELD) score of ≥15 (Model for End-stage Liver Disease (MELD) score 15-19, HR 5.46, 95% CI 1.81 to 16.50; MELD score≥20, HR 5.24, 95% CI 1.77 to 15.55) and dyspnoea on presentation (HR 3.89, 95% CI 2.02 to 7.51) being the two negative independent factors for mortality. Twenty-six patients underwent an LT after a median time of 78.5 (IQR 44-102) days, and 25 (96%) were alive after a median follow-up of 118 days (IQR 31-170). CONCLUSIONS: Increased mortality in LT candidates with COVID-19 (32.7%), reaching 45% in those with decompensated cirrhosis (DC) and Lab-MELD score of ≥15, was observed, with no significant difference between first and second waves of the pandemic. Respiratory failure was the major cause of death. The dismal prognosis of patients with DC supports the adoption of strict preventative measures and the urgent testing of vaccination efficacy in this population. Prior SARS-CoV-2 symptomatic infection did not affect early post-transplant survival (96%).

Long Term Follow-up of Liver Transplant Recipients: Considerations for Non-transplant Specialists.

Patient and liver graft survival rates have improved significantly in the last decades, leading to complications mainly related to long-term immunosuppression. Prevention of, screening for metabolic syndrome, cardiovascular disease, de novo diabetes mellitus, renal dysfunction, and malignancies and their management are mandatory due to important causes of morbidity and mortality in this patient population. Quality of life (QoL) and functional benefits are clearly better compared to preoperative status; however, post-liver transplantation (LT) complications may impair and alter QoL scores. Individualized immunosuppression managed by transplant physicians and collaboration with other non-transplant specialists for recognition and treatment of medical complications and comorbidities after LT is the key to enhanced QoL and life expectancy of this patient population.

Phenotypic assessment of liver-derived cell cultures during in vitro expansion.

Background: Liver cells represent an attractive source of cells for autologous regenerative medicine. The present study assesses the liver cells' stability during in vitro expansion, as a prerequisite for therapeutic use. Results: The human liver cell cultures in this study were propagated efficiently in vitro for at least 12 passages. No significant changes in morphology, intracellular ultrastructures and characteristic markers expression were found during in vitro expansion of cells from all analyzed donors. However, expanded cells derived from male donors of >60 years old, lost the Y chromosome. Conclusion: Liver-derived cell cultures adopt a proliferative, stable mesenchymal phenotype, through an epithelial to mesenchymal transition process. The molecular and phenotypic changes of the cells during propagation are uniform, despite the heterogeneity of the different donors. Loss of Y chromosome occurs after cells' propagation in elder male donors.

Genetic and Life Style Risk Factors for Recurrent Non-alcoholic Fatty Liver Disease Following Liver Transplantation.

Recurrent or de novo non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) following liver transplantation (LT) is a frequent event being increasingly recognized over the last decade, but the influence of recurrent NASH on graft and patient outcomes is not yet established. Taking into consideration the long term survival of liver transplanted patients and long term complications with associated morbidity and mortality, it is important to define and minimize risk factors for recurrent NAFLD/NASH. Metabolic syndrome, obesity, dyslipidemia, diabetes mellitus are life style risk factors that can be potentially modified by various interventions and thus, decrease the risk of recurrent NAFLD/NASH. On the other hand, genetic factors like recipient and/or donor PNPLA3, TM6SF2, GCKR, MBOAT7 or ADIPOQ gene polymorphisms proved to be risk factors for recurrent NASH. Personalized interventions to influence the different metabolic disorders occurring after LT in order to minimize the risks, as well as genetic screening of donors and recipients should be performed pre-LT in order to achieve diagnosis and treatment as early as possible.