Post-treatment LSM rather than change during treatment predicts decompensation in patients with cACLD after HCV cure.

BACKGROUND & AIMS: Baveno VII has defined a clinically significant (i.e., prognostically meaningful) liver stiffness measurement (LSM)-decrease in cACLD by ≥20% associated with a final LSM<20 kPa, or any decrease to <10 kPa. However, these rules have not yet been validated against direct clinical endpoints. METHODS: We retrospectively analysed cACLD patients (LSM≥10 kPa) with paired liver stiffness measurement (LSM) before (BL) and after (FU) HCV-cure by interferon-free therapies from 15 European centers. The cumulative incidence of hepatic decompensation was compared according to these criteria, considering hepatocellular carcinoma and non-liver-related death as competing risks. RESULTS: 2335 patients followed for a median of 6 years were analysed. Median BL-LSM was 16.6 kPa with 37.1% having ≥20 kPa. After HCV-cure, FU-LSM decreased to a median of 10.9 kPa (<10 kPa: 1002 [42.9%], ≥20 kPa: 465 [19.9%]) translating into a median LSM-change of -5.3 (-8.8-[-2.4])kPa corresponding to -33.9 (-48.0-[-15.9])%. Patients achieving a clinically significant decrease (65.4%) had a significantly lower risk of hepatic decompensation (subdistribution hazard ratio [SHR]: 0.12 [95%CI: 0.04-0.35], p<0.001). However, these risk differences were primarily driven by a negligible risk in patients with FU-LSM <10 kPa (5y-cumulative incidence: 0.3%) compared to a high risk in patients with FU-LSM ≥20 kPa (16.6%). Patients with FU-LSM 10-19.9 kPa (37.4%) also had a low risk of hepatic decompensation (5y-cumulative incidence: 1.7%), and importantly, the risk of hepatic decompensation did not differ between those with/without an LSM-decrease ≥20% (p=0.550). CONCLUSIONS: FU-LSM is key for risk stratification after HCV-cure and should guide clinical decision-making. LSM dynamics do not hold significant prognostic information in patients with FU-LSM 10-19.9 kPa, and thus, their consideration is not of sufficient incremental value in the specific context of HCV-cure.

Clinical outcomes and prognostic factors after HCV clearance with DAA in HIV/HCV coinfected patients with advanced Fibrosis/Cirrhosis.

AIMS AND BACKGROUND: We assessed long-term clinical outcomes and prognostic factors for liver disease progression after sustained viral response (SVR) with direct-acting antivirals (DAAs) in HIV/HCV coinfected patients with advanced fibrosis (AdF) or cirrhosis. APPROACH AND RESULTS: A total of 1,300 patients who achieved SVR with DAAs from 2014 to 2017 in Spain were included: 1145 with chronically advanced liver disease (cACLD) (384 AdF and 761 compensated cirrhosis [CoC]) and 155 with decompensated cirrhosis (DeC). The median follow-up was 40.9 months. Overall, 85 deaths occurred, 61 due to non-liver non-AIDS-related (NLNA) causes that were the leading cause of death across all stages of liver disease. The incidence (95% confidence interval [CI]) of decompensation per 100 person-years (py) was 0 in patients with AdF, 1.01 (0.68-1.51) in patients with CoC, and 8.35 (6.05-11.53) in patients with DeC. The incidence (95% CI) of hepatocellular carcinoma (HCC) per 100 py was 0.34 (0.13-0.91) in patients AdF, 0.73 (0.45-1.18) in patients with CoC, and 1.92 (1.00-3.70) per 100 py in patients with DeC. Prognostic factors for decompensation in patients with cACLD included serum albumin, liver stiffness measurement (LSM), and FIB-4. In this population, LSM and LSM-based posttreatment risk stratification models showed their predictive ability for decompensation and HCC. CONCLUSIONS: NLNA events were the leading causes of morbidity and mortality after DAA cure among coinfected patients with AdF/cirrhosis. Among those with cACLD, baseline LSM and posttreatment LSM-based models helped to assess decompensation and HCC risk.

Hepatic hemodynamic study: More than just HVPG measurement.

Evaluation and staging of liver disease is essential in the clinical decision-making process of liver tumors. The severity of portal hypertension (PH) is the main prognostic factor in advanced liver disease. Performing an accurate hepatic venous pressure gradient (HVPG) measurement is not always possible, especially when veno-venous communications are present. In those complex cases, a refinement in HVPG measurement with a thorough evaluation of each of the components of PH is mandatory. We aimed at describing how some technical modifications and complementary procedures may contribute to an accurate and complete clinical evaluation to improve therapeutic decisions.

Portal hypertension increases the risk of hepatic decompensation after 90Yttrium radioembolization in patients with hepatocellular carcinoma: a cohort study.

Background: Transarterial radioembolization (TARE) is increasingly used in patients with hepatocellular carcinoma (HCC). This treatment can induce or impair portal hypertension, leading to hepatic decompensation. TARE also promotes changes in liver and spleen volumes that may modify therapeutic decisions and outcomes after therapy. Objectives: We aimed to investigate the impact of TARE on the incidence of decompensation events and its predictive factors. Design: In all, 63 consecutive patients treated with TARE between February 2012 and December 2018 were retrospectively included. Methods: We assessed clinical (including Barcelona Clinic Liver Cancer stage, portal hypertension assessment, and liver decompensation), laboratory parameters, and liver and spleen volumes before and 6 and 12 weeks after treatment. A multivariate analysis was performed. Results: In total, 18 out of 63 (28.6%) patients had liver decompensation (ascites, variceal bleeding, jaundice, or encephalopathy) within the first 3 months after therapy, not associated with tumor progression. Clinically significant portal hypertension (CSPH) and bilobar treatment independently predicted the development of liver decompensation after TARE. A significant volume increase in the non-treated hemi-liver was observed only in patients with unilobar treatment (median volume increase of 20.2% in patients with right lobe TARE; p = 0.007), especially in those without CSPH. Spleen volume also increased after TARE (median volume increase of 16.1%; p = 0.0001) and was associated with worsening liver function scores and decreased platelet count. Conclusion: Bilobar TARE and CSPH may be associated with an increased risk of liver decompensation in patients with intermediate or advanced HCC. A careful assessment considering these variables before therapy may optimize candidate selection and improve treatment planning.

Neuroblastoma RAS viral oncogene homolog (N-RAS) deficiency aggravates liver injury and fibrosis.

Progressive hepatic damage and fibrosis are major features of chronic liver diseases of different etiology, yet the underlying molecular mechanisms remain to be fully defined. N-RAS, a member of the RAS family of small guanine nucleotide-binding proteins also encompassing the highly homologous H-RAS and K-RAS isoforms, was previously reported to modulate cell death and renal fibrosis; however, its role in liver damage and fibrogenesis remains unknown. Here, we approached this question by using N-RAS deficient (N-RAS-/-) mice and two experimental models of liver injury and fibrosis, namely carbon tetrachloride (CCl4) intoxication and bile duct ligation (BDL). In wild-type (N-RAS+/+) mice both hepatotoxic procedures augmented N-RAS expression in the liver. Compared to N-RAS+/+ counterparts, N-RAS-/- mice subjected to either CCl4 or BDL showed exacerbated liver injury and fibrosis, which was associated with enhanced hepatic stellate cell (HSC) activation and leukocyte infiltration in the damaged liver. At the molecular level, after CCl4 or BDL, N-RAS-/- livers exhibited augmented expression of necroptotic death markers along with JNK1/2 hyperactivation. In line with this, N-RAS ablation in a human hepatocytic cell line resulted in enhanced activation of JNK and necroptosis mediators in response to cell death stimuli. Of note, loss of hepatic N-RAS expression was characteristic of chronic liver disease patients with fibrosis. Collectively, our study unveils a novel role for N-RAS as a negative controller of the progression of liver injury and fibrogenesis, by critically downregulating signaling pathways leading to hepatocyte necroptosis. Furthermore, it suggests that N-RAS may be of potential clinical value as prognostic biomarker of progressive fibrotic liver damage, or as a novel therapeutic target for the treatment of chronic liver disease.

Non-invasive candidate protein signature predicts hepatic venous pressure gradient reduction in cirrhotic patients after sustained virologic response.

BACKGROUND AND AIMS: A reduction in hepatic venous pressure gradient (HVPG) is the most accurate marker for assessing the severity of portal hypertension and the effectiveness of intervention treatments. This study aimed to evaluate the prognostic potential of blood-based proteomic biomarkers in predicting HVPG response amongst cirrhotic patients with portal hypertension due to Hepatitis C virus (HCV) and had achieved sustained virologic response (SVR). METHODS: The study comprised 59 patients from two cohorts. Patients underwent paired HVPG (pretreatment and after SVR), liver stiffness (LSM), and enhanced liver fibrosis scores (ELF) measurements, as well as proteomics-based profiling on serum samples using SomaScan® at baseline (BL) and after SVR (EOS). Machine learning with feature selection (Caret, Random Forest and RPART) methods were performed to determine the proteins capable of classifying HVPG responders. Model performance was evaluated using AUROC (pROC R package). RESULTS: Patients were stratified by a change in HVPG (EOS vs. BL) into responders (greater than 20% decline in HVPG from BL, or <10 mmHg at EOS with >10 mmHg at BL) and non-responders. LSM and ELF decreased markedly after SVR but did not correlate with HVPG response. SomaScan (SomaLogic, Inc., Boulder, CO) analysis revealed a substantial shift in the peripheral proteome composition, reflected by 82 significantly differentially abundant proteins. Twelve proteins accurately distinguished responders from non-responders, with an AUROC of .86, sensitivity of 83%, specificity of 83%, accuracy of 83%, PPV of 83%, and NPV of 83%. CONCLUSIONS: A combined non-invasive soluble protein signature was identified, capable of accurately predicting HVPG response in HCV liver cirrhosis patients after achieving SVR.

Role of EpCAM+ CD133+ extracellular vesicles in steatosis to steatohepatitis transition in NAFLD.

BACKGROUND AND AIMS: Extracellular vesicles (EVs) have emerged as a potential source of circulating biomarkers in liver disease. We evaluated circulating AV+ EpCAM+ CD133+ EVs as a potential biomarker of the transition from simple steatosis to steatohepatitis. METHODS: EpCAM and CD133 liver proteins and EpCAM+ CD133+ EVs levels were analysed in 31 C57BL/6J mice fed with a chow or high fat, high cholesterol and carbohydrates diet (HFHCC) for 52 weeks. The hepatic origin of MVs was addressed using AlbCrexmT/mG mice fed a Western (WD) or Dual diet for 23 weeks. Besides, we assessed plasma MVs in 130 biopsy-proven NAFLD patients. RESULTS: Hepatic expression of EpCAM and CD133 and EpCAM+ CD133+ EVs increased during disease progression in HFHCC mice. GFP+ MVs were higher in AlbCrexmT/mG mice fed a WD (5.2% vs 12.1%) or a Dual diet (0.5% vs 7.3%). Most GFP+ MVs were also positive for EpCAM and CD133 (98.3% and 92.9% respectively), suggesting their hepatic origin. In 71 biopsy-proven NAFLD patients, EpCAM+ CD133+ EVs were significantly higher in those with steatohepatitis compare to those with simple steatosis (286.4 ± 61.9 vs 758.4 ± 82.3; p < 0.001). Patients with ballooning 367 ± 40.6 vs 532.0 ± 45.1; p = 0.01 and lobular inflammation (321.1 ± 74.1 vs 721.4 ± 80.1; p = 0.001), showed higher levels of these EVs. These findings were replicated in an independent cohort. CONCLUSIONS: Circulating levels of EpCAM+ CD133+ MVs in clinical and experimental NAFLD were increased in the presence of steatohepatitis, showing high potential as a non-invasive biomarker for the evaluation and management of these patients.

Pregnancy outcomes in patients with portal cavernoma: A case series study.

OBJECTIVE: Non-cirrhotic portal vein cavernoma (PVC) is a cause of portal hypertension (PH) frequently affecting women of childbearing age. Cavernous transformation of the portal vein is frequently associated with prothrombotic disorders and often entails multiple hemodynamic changes, porto-collateral shunt development and thrombopenia, all of which can affect the course of pregnancy. Our aim was to evaluate the risk of PH-related complications and pregnancy outcomes in patients with PVC. METHODS: Retrospective case series study of patients with PVC undergoing pregnancy in a tertiary care hospital. RESULTS: Eight pregnancies fulfilled the eligibility criteria. All patients had a predisposing factor for PVC. One episode of variceal bleeding was reported at week 28. Six cesarean sections were scheduled to avoid labor while two urgent surgeries were indicated due to fetal distress and intrauterine growth restriction (IUGR). In all but one case, anticoagulation was prescribed after delivery. No hemorrhagic or thrombotic complications were reported. There were four cases of IUGR with no case of miscarriage or stillbirth. CONCLUSION: Pregnancy in patients with PVC has an overall favorable outcome albeit a higher risk of PH-derived complications, and IUGR may be expected. Hence, PVC must not be considered a contraindication for pregnancy although larger prospective studies are necessary.

An Economic Analysis of Transjugular Intrahepatic Portosystemic Covered Stent Shunt for Variceal Bleeding and Refractory Ascites in a Spanish Setting.

INTRODUCTION: The primary aim is to estimate the cost-effectiveness of transjugular intrahepatic portosystemic stent shunt (TIPSS) in two indications from a Spanish perspective. Firstly, as pre-emptive treatment for patients with acute variceal bleeding (indication 1) compared with endoscopic band ligation plus drug therapy. Secondly, to treat refractory ascites (indication 2) compared with large volume paracentesis. METHODS: A two-state (alive and dead) Markov model was developed to capture the costs and health impact for the two indications over a 2-year time horizon with monthly cycles. In the alive state, patients could experience adverse event(s), associated with costs and disutility, such as recurrent variceal bleeding, ascites, and hepatic encephalopathy. Discount rates of 3% for utilities and costs and a cost-effectiveness threshold of €25,000 per QALY were applied. RESULTS: In the base case analysis, TIPSS was estimated to be cost-effective as a pre-emptive treatment for indication 1 (incremental cost and QALYs of - €230 and 0.211, respectively). TIPSS also remained cost-effective (€16,819/QALY) in a conservative scenario analysis, conducted with an alternate source for clinical parameters. The key drivers of the outcomes were survival for the comparator arm, mean band ligation outpatient procedures, and TIPSS treatment costs. TIPSS was estimated to dominate the comparator for indication 2 (incremental cost and QALYs of - €25,687 and 0.531, respectively). The key drivers of the outcomes were monthly paracentesis sessions and cost per inpatient stay for those undergoing paracentesis. CONCLUSIONS: TIPSS is likely to be a cost-effective and a cost-saving treatment in patients with cirrhosis in indications 1 and 2, compared with standard treatments. The analyses estimate clinical benefits along with reduced healthcare costs from avoided downstream resource consumption.

Alcohol-related liver disease phenotype impacts survival after an acute variceal bleeding episode.

BACKGROUND & AIMS: Alcohol-related hepatitis (AH) encompasses a high mortality. AH might be a concomitant event in patients with acute variceal bleeding (AVB). The current study aimed to assess the prevalence of AH in patients with AVB and to compare the clinical outcomes of AH patients to other alcohol-related liver disease (ALD) phenotypes and viral cirrhosis. METHODS: Multicentre, observational study including 916 patients with AVB falling under the next categories: AH (n = 99), ALD cirrhosis actively drinking (d-ALD) (n = 285), ALD cirrhosis abstinent from alcohol (a-ALD) (n = 227) and viral cirrhosis (n = 305). We used a Cox proportional hazards model to calculate adjusted hazard ratio (HR) of death adjusted by MELD. RESULTS: The prevalence of AH was 16% considering only ALD patients. AH patients exhibited more complications. Forty-two days transplant-free survival was worse among AH, but statistical differences were only observed between AH and d-ALD groups (84 vs. 93%; p = 0.005), when adjusted by MELD no differences were observed between AH and the other groups. At one-year, survival of AH patients (72.7%) was similar to the other groups; when adjusted by MELD mortality HR was better in AH compared to a-ALD (0.48; 0.29-0.8, p = 0.004). Finally, active drinkers who remained abstinent presented better survival, independently of having AH. CONCLUSIONS: Contrary to expected, AH patients with AVB present no worse one-year survival than other patients with different alcohol-related phenotypes or viral cirrhosis. Abstinence influences long-term survival and could explain these counterintuitive results.

Lack of Cyclin E1 in hepatocytes aggravates ethanol-induced liver injury and hepatic steatosis in experimental murine model of acute and chronic alcohol-associated liver disease.

BACKGROUND: Cyclin E1 is the regulatory subunit of cyclin-dependent kinase 2 (Cdk2) and one of the central players in cell cycle progression. We recently showed its crucial role for initiation of liver fibrosis and hepatocarcinogenesis. In the present study, we investigated the role of Cyclin E1 in the development of alcohol-associated liver disease (ALD). METHODS: Mice with constitutive (E1-/-), hepatocyte-specific (Cyclin E1Δhepa), or intestinal-epithelial-cell-specific (Cyclin E1ΔIEC) inactivation of Cyclin E1 and corresponding wild type littermate controls (WT) were administered either a Lieber-DeCarli ethanol diet (LDE) for 3 weeks or acute ethanol binges (6 g/kg) through oral gavage. Serum parameters of liver functionality were measured; hepatic tissues were collected for biochemical and histological analyses. RESULTS: The administration of acute EtOH binge and chronic LDE diet to E1-/- mice enhanced hepatic steatosis, worsened liver damage and triggered body weight loss. Similarly, in the acute EtOH binge model, Cyclin E1Δhepa mice revealed a significantly worsened liver phenotype. In contrast, inactivation of Cyclin E1 only in intestinal epithelial cell (IECs)did not lead to any significant changes in comparison to WT mice after acute EtOH challenge. Remarkably, both acute and chronic EtOH administration in E1-/- animals resulted in increased levels of ADH and decreased expression of ALDH1/2. The additional application of a pan-Cdk inhibitor (S-CR8) further promoted liver damage in EtOH-treated WT mice. CONCLUSION: Our data point to a novel unexpected role of Cyclin E1 in hepatocytes for alcohol metabolism, which seems to be independent of the canonical Cyclin E1/Cdk2 function as a cell cycle regulator.

Metabolomics as a tool to predict the risk of decompensation or liver-related death in patients with compensated cirrhosis.

BACKGROUND AND AIMS: Patients with compensated cirrhosis with clinically significant portal hypertension (CSPH: HVPG > 10 mm Hg) have a high risk of decompensation. HVPG is, however, an invasive procedure not available in all centers. The present study aims to assess whether metabolomics can improve the capacity of clinical models in predicting clinical outcomes in these compensated patients. APPROACH AND RESULTS: This is a nested study from the PREDESCI cohort (an RCT of nonselective beta-blockers vs. placebo in 201 patients with compensated cirrhosis and CSPH), including 167 patients for whom a blood sample was collected. A targeted metabolomic serum analysis, using ultra-high-performance liquid chromatography-mass spectrometry, was performed. Metabolites underwent univariate time-to-event cox regression analysis. Top-ranked metabolites were selected using Log-Rank p -value to generate a stepwise cox model. Comparison between models was done using DeLong test. Eighty-two patients with CSPH were randomized to nonselective beta-blockers and 85 to placebo. Thirty-three patients developed the main endpoint (decompensation/liver-related death). The model, including HVPG, Child-Pugh, and treatment received ( HVPG/Clinical model ), had a C-index of 0.748 (CI95% 0.664-0.827). The addition of 2 metabolites, ceramide (d18:1/22:0) and methionine (HVPG/Clinical/Metabolite model), significantly improved the model's performance [C-index of 0.808 (CI95% 0.735-0.882); p =0.032]. The combination of these 2 metabolites together with Child-Pugh and the type of treatment received (Clinical/Metabolite model) had a C-index of 0.785 (CI95% 0.710-0.860), not significantly different from the HVPG-based models including or not metabolites. CONCLUSIONS: In patients with compensated cirrhosis and CSPH, metabolomics improves the capacity of clinical models and achieves similar predictive capacity than models including HVPG.

Sympathetic nervous activation, mitochondrial dysfunction and outcome in acutely decompensated cirrhosis: the metabolomic prognostic models (CLIF-C MET).

BACKGROUND AND AIMS: Current prognostic scores of patients with acutely decompensated cirrhosis (AD), particularly those with acute-on-chronic liver failure (ACLF), underestimate the risk of mortality. This is probably because systemic inflammation (SI), the major driver of AD/ACLF, is not reflected in the scores. SI induces metabolic changes, which impair delivery of the necessary energy for the immune reaction. This investigation aimed to identify metabolites associated with short-term (28-day) death and to design metabolomic prognostic models. METHODS: Two prospective multicentre large cohorts from Europe for investigating ACLF and development of ACLF, CANONIC (discovery, n=831) and PREDICT (validation, n=851), were explored by untargeted serum metabolomics to identify and validate metabolites which could allow improved prognostic modelling. RESULTS: Three prognostic metabolites strongly associated with death were selected to build the models. 4-Hydroxy-3-methoxyphenylglycol sulfate is a norepinephrine derivative, which may be derived from the brainstem response to SI. Additionally, galacturonic acid and hexanoylcarnitine are associated with mitochondrial dysfunction. Model 1 included only these three prognostic metabolites and age. Model 2 was built around 4-hydroxy-3-methoxyphenylglycol sulfate, hexanoylcarnitine, bilirubin, international normalised ratio (INR) and age. In the discovery cohort, both models were more accurate in predicting death within 7, 14 and 28 days after admission compared with MELDNa score (C-index: 0.9267, 0.9002 and 0.8424, and 0.9369, 0.9206 and 0.8529, with model 1 and model 2, respectively). Similar results were found in the validation cohort (C-index: 0.940, 0.834 and 0.791, and 0.947, 0.857 and 0.810, with model 1 and model 2, respectively). Also, in ACLF, model 1 and model 2 outperformed MELDNa 7, 14 and 28 days after admission for prediction of mortality. CONCLUSIONS: Models including metabolites (CLIF-C MET) reflecting SI, mitochondrial dysfunction and sympathetic system activation are better predictors of short-term mortality than scores based only on organ dysfunction (eg, MELDNa), especially in patients with ACLF.

Tenofovir Disoproxil Fumarate Reduces the Severity of COVID-19 in Patients with Chronic Hepatitis B.

BACKGROUND AND AIMS: HIV-positive patients on tenofovir hydroxyl fumarate (TDF)/emtricitabine have a lower risk of COVID-19 and hospitalization than those given other treatments. Our aim was to analyze the severity of COVID-19 in patients with chronic hepatitis B (CHB) on TDF or entecavir (ETV). METHODS: Spanish hospital databases (n = 28) including information regarding adult CHB patients on TDF or ETV for the period February 1st to November 30th 2020 were searched for COVID-19, defined as a positive SARS-CoV-2 polymerase chain reaction, and for severe COVID-19. RESULTS: Of 4736 patients, 117 had COVID-19 (2.5%), 67 on TDF and 50 on ETV. Compared to patients on TDF, those on ETV showed (p < 0.05) greater rates of obesity, diabetes, ischemic cardiopathy, and hypertension. COVID-19 incidence was similar in both groups (2.3 vs. 2.6%). Compared to TDF, patients on ETV more often (p < 0.01) had severe COVID-19 (36 vs. 6%), required intensive care unit (ICU) (10% vs. 0) or ventilatory support (20 vs. 3%), were hospitalized for longer (10.8 ± 19 vs. 3.1 ± 7 days) or died (10 vs. 1.5%, p = 0.08). In an IPTW propensity score analysis adjusted for age, sex, obesity, comorbidities, and fibrosis stage, TDF was associated with a sixfold reduction in severe COVID-19 risk (adjusted-IPTW-OR 0.17, 95%CI 0.04-0.67, p = 0.01). CONCLUSION: Compared to ETV, TDF seems to play a protective role in CHB patients with SARS-CoV-2 whereby the risk of severe COVID-19 is lowered.

CT-derived liver and spleen volume accurately diagnose clinically significant portal hypertension in patients with hepatocellular carcinoma.

Background & Aims: Clinically significant portal hypertension (CSPH) is a landmark in the natural history of cirrhosis, influencing clinical decisions in patients with hepatocellular carcinoma (HCC). Previous small series suggested that splanchnic volume measurements may predict portal hypertension. We aimed to evaluate whether volumetry obtained by standard multidetector computerised tomography (MDCT) can predict CSPH in patients with HCC. Methods: We included 175 patients with HCC, referred for hepatic venous pressure gradient (HVPG) evaluation, in whom contemporary MDCT was available. Liver volume, spleen volume (SV) and liver segmental volume ratio (LSVR: volume of the segments I-III/volume of the segments IV-VIII) were calculated semi-automatically from MDCT. Other non-invasive tests (NITs) were also employed. Results: Volume parameters could be measured in almost 100% of cases with an excellent inter-observer agreement (intraclass correlation coefficient >0.950). SV and LSVR were independently associated with CSPH (HVPG ≥10 mmHg) and did not interact with aetiology. The volume Index (VI), calculated as the product of SV and LSVR, predicted CSPH (AUC 0.83; 95% CI 0.77-0.89). Similar results were observed in an external cohort (n = 23) (AUC 0.87; 95% CI 0.69-1.00). Setting a sensitivity and specificity of 98%, VI could have avoided 35.9% of HVPG measurements. The accuracy of VI was similar to that of other NITs. VI also accurately predicted HVPG greater than 12, 14, 16 and 18 mmHg (AUC 0.81 [95% CI 0.74-0.88], 0.84 [95% CI 0.77-0.91], 0.85 [95% CI 0.77-0.92] and 0.87 [95% CI 0.79-0.94], respectively). Conclusions: Quantification of liver and spleen volumes by MDCT is a simple, accurate and reliable method of CSPH estimation in patients with compensated cirrhosis and HCC. Impact and implications: An increase in portal pressure strongly impacts outcomes after surgery in patients with early hepatocellular carcinoma (HCC). Direct measurement through hepatic vein catheterization remains the reference standard for portal pressure assessment, but its invasiveness limits its application. Therefore, we evaluated the ability of CT scan-based liver and spleen volume measurements to predict portal hypertension in patients with HCC. Our results indicate that the newly described index, based on quantification of liver and spleen volume, accurately predicts portal hypertension. These results suggest that a single imaging test may be used to diagnose and stage HCC, while providing an accurate estimation of portal hypertension, thus helping to stratify surgical risks.

Implementation and impact of an antibiotic control program and multidrug-resistant bacterial colonization in a liver transplant unit.

INTRODUCTION: infections by multidrug-resistant bacteria are a major cause of morbidity and mortality in transplant patients. OBJECTIVE: a retrospective single-center study was performed to evaluate the implementation of an Antimicrobial Treatment Optimization Program (PROA) on multidrug-resistant bacteria colonization and infection after liver transplant (LT). METHODS: colonization by multidrug-resistant bacteria and infections during the first year after a liver transplant were analyzed in a group of 76 transplanted patients in two stages, before and after PROA (2016-2019). Clinical variables related to infection, readmissions and survival one year after the liver transplant were analyzed. RESULTS: there was good adherence to the PROA. Infection was the most frequent cause for readmission during the first year after the liver transplant. Incidence of infections was similar during both periods (mean of 1.25 and 1.5 episodes of bacterial infection per patient/year, respectively) with 19 bacterial infectious episodes, six by hospital-acquired multidrug-resistant and extensively drug-resistant (MDR-XDR) bacteria in the pre-PROA stage, and 18 bacterial infectious episodes, five by MDR-XDR in the post-PROA stage. A 37 % decrease of post-TH of rectal colonization by MDR-XDR after liver transplant was observed during 2019. CONCLUSIONS: epidemiological surveillance policies and antibiotic optimization are key to control the increase of colonization and infection by multidrug-resistant bacteria in liver transplant units. Long-term studies are needed to better evaluate the impact of these programs.

Prognostic implications of systolic function in patients with cirrhosis.

INTRODUCTION: LV intrinsic systolic cardiac function in cirrhotic patients is conditioned by the degree of sympathetic activation and the use of non-selective beta-blockers (NSBBs). Systolic function can be non-invasively measured by ultrasound using Ejection Intraventricular Pressure Differences in the LV (EIVPD). We aimed to address the relationship between systolic function and long-term clinical outcomes using EIVPD. METHODS: We studied 45 Child-Pugh B or C patients (13 female, 24 on NSBBs) using echocardiography. The primary endpoint was the combination of any-cause mortality or liver transplantation. After a follow-up of 7 years (796 person-months) and a median period of 17 (10-42) months, 41 patients (91%) reached the primary endpoint: 13 (29%) died and 28 (62%) underwent transplantation. RESULTS: By univariable analysis the primary endpoint was related exclusively to MELD score. However, in a multivariable proportional-hazards analysis, adjusted for age, sex and MELD score, EIVPD was inversely related to the primary endpoint, showing interaction with NSBBs. In patients without NSBBs, EIVPD inversely predicted the primary endpoint, whereas in patients with NSBBs, EIVPD was unrelated to outcomes. These relationships were undetected by myocardial strain or conventional cardiac indices. CONCLUSIONS: LV intrinsic systolic function, as noninvasively measured by EIVPD is a predictor of long-term outcomes in patients with cirrhosis. The prognostic value of EIVPD is present along any degree of liver dysfunction but blunted by NSBBs. Because NSBBs have a deep effect on myocardial contractility, these drugs need to be considered when assessing the prognostic implications of cardiac function in these patients.

Hepatic encephalopathy is not a contraindication to pre-emptive TIPS in high-risk patients with cirrhosis with variceal bleeding.

BACKGROUND: A pre-emptive transjugular intrahepatic portosystemic shunt (pTIPS) reduces mortality in high-risk patients with cirrhosis (Child-Pugh C/B+active bleeding) with acute variceal bleeding (AVB). Real-life studies point out that <15% of patients eligible for pTIPS ultimately undergo transjugular intrahepatic portosystemic shunt (TIPS) due to concerns about hepatic encephalopathy (HE). The outcome of patients undergoing pTIPS with HE is unknown. We aimed to (1) assess the prevalence of HE in patients with AVB; (2) evaluate the outcome of patients presenting HE at admission after pTIPS; and (3) determine if HE at admission is a risk factor for death and post-TIPS HE. PATIENTS AND METHODS: This is an observational study including 2138 patients from 34 centres between October 2011 and May 2015. Placement of pTIPS was based on individual centre policy. Patients were followed up to 1 year, death or liver transplantation. RESULTS: 671 of 2138 patients were considered at high risk, 66 received pTIPS and 605 endoscopic+drug treatment. At admission, HE was significantly more frequent in high-risk than in low-risk patients (39.2% vs 10.6%, p<0.001). In high-risk patients with HE at admission, pTIPS was associated with a lower 1-year mortality than endoscopic+drug (HR 0.374, 95% CI 0.166 to 0.845, p=0.0181). The incidence of HE was not different between patients treated with pTIPS and endoscopic+drug (38.2% vs 38.7%, p=0.9721), even in patients with HE at admission (56.4% vs 58.7%, p=0.4594). Age >56, shock, Model for End-Stage Liver Disease score >15, endoscopic+drug treatment and HE at admission were independent factors of death in high-risk patients. CONCLUSION: pTIPS is associated with better survival than endoscopic treatment in high-risk patients with cirrhosis with variceal bleeding displaying HE at admission.

Metabolic-associated fatty liver disease: From simple steatosis toward liver cirrhosis and potential complications. Proceedings of the Third Translational Hepatology Meeting, organized by the Spanish Association for the Study of the Liver (AEEH) / Enfermedad del hígado graso asociado al metabolismo: de la simple esteatosis a la cirrosis hepática y sus posibles complicaciones. Actas de la Tercera Reunión de Hepatología Traslacional, organizada por la Asociación Española para el Estudio del Hígado (AEEH)

This is a meeting report of the 3rd Translational Hepatology Meeting held in Alicante, Spain, in October 2021. The meeting, which was organized by the Spanish Association for the Study of the Liver (AEEH), provided an update on the recent advances in the field of basic and translational hepatology, with a particular focus on the molecular and cellular mechanisms and therapeutic targets involved in metabolic-associated fatty liver disease (MAFLD), metabolic-associated steatohepatitis (MASH), cirrhosis and end-stage hepatocellular carcinoma (HCC).(AU)

Este es el resumen de la 3ª Reunión de Hepatología Traslacional celebrada en Alicante, España, en octubre de 2021. La reunión, organizada por la Asociación Española para el Estudio del Hígado (AEEH), ofreció una actualización de los recientes avances en el campo de la Hepatología básica y traslacional, con un enfoque en los mecanismos moleculares y celulares y las dianas terapéuticas implicadas en la enfermedad del hígado graso asociada a disfunción metabólica (MAFLD), la esteatohepatitis asociada a disfunción metabólica (MASH), y las etapas terminales como la cirrosis y el carcinoma hepatocelular (HCC).(AU)