Risk Of Decompensation Research Articles

Bacterial infection adversely increases the risk of decompensation in patients with hepatitis B virus-related compensated cirrhosis: a retrospective study

BackgroundHepatitis B virus related compensated cirrhosis generally has a favorable prognosis until decompensation occurs. Bacterial infections are prevalent in Hepatitis B virus related decompensated cirrhosis.Bacterial infection and decompensated hepatitis B cirrhosis are mutually reinforcing. And it also interacts with and promotes certain decompensation-related events. However, the impact of bacterial infections on the progression from compensated to decompensated cirrhosis in Hepatitis B patients remains unclear.MethodsWe retrospectively analyzed the baseline characteristics of 1,011 patients with Hepatitis B virus related compensated cirrhosis. Using time-dependent regression analysis, we evaluated whether bacterial infections increase the risk of decompensation, defined as the occurrence of ascites, hepatic encephalopathy, or variceal bleeding.ResultsA total of 1,011 patients were retrospectively analyzed over a median follow-up period of 79 months. Bacterial infections were observed in 89 patients (8.8%). Respiratory and urinary tract infections were the most common bacterial infections.Decompensation occurred in 44.9% of patients with bacterial infections, compared to 9% of those without BIs. Patients with bacterial infections had a higher risk of decompensation ([OR] 1.024; 95% CI 1.016–1.032; p < 0.001) than those without bacterial infections.ConclusionOur findings suggest that bacterial infections have a significant impact on the progression of hepatitis B virus related compensated cirrhosis, notably increasing the risk of decompensation.

Validation and expansion of Baveno VII criteria for cACLD and CSPH based on liver stiffness and platelet count: Correlation with risk of hepatic decompensation and death.

Recently proposed "Rule-of-Five" criteria define compensated advanced chronic liver disease (cACLD) and clinically significant portal hypertension (CSPH) using liver stiffness (LS) and platelet count. We aimed to validate these criteria by determining whether they are associated with risk of adverse outcomes. Patients without prior hepatic decompensation or hepatocellular carcinoma (HCC) who underwent LS and platelet measurements (n=17,076), were categorized as follows: no cACLD (LS 2.5-9.9 kPa); probable cACLD (LS 10-14.9 kPa); certain cACLD-no CSPH (LS 15-19.9 kPa and platelets ≥110,000/µL or LS 20-24.9 kPa and platelets ≥150,000/µL); probable CSPH (LS 15-19.9 kPa and platelets <110,000/µL or LS 20-24.9 and platelets <150,000/µL); and certain CSPH (LS ≥25 Kpa), which we further sub-divided into 25-49.9 kPa and 50-75 kPa.During a median follow-up of 2.82 years, each increase in "Rule-of-Five" category was associated linearly with higher risks of death (hazard ratio [HR] 1.22, 95% CI 1.18-1.25) and decompensation (HR 1.52, 95% CI 1.46-1.58). Compared to patients with LS 25-49.9 kPa, those with LS 50-75 kPa ("critical" CSPH) had approximately double the risk of decompensation (11.24 vs. 4.20 per 100 patient-years) and death (9.85 vs. 6.98 per 100 patient-years). The Baveno VII "Rule-of-Five" criteria provide a valid system for stratifying risks of death and hepatic decompensation and should be used routinely in patients with chronic liver disease. Among patients with CSPH (LS ≥25 kPa), the subgroup with LS 50-75 kPa ("critical" CSPH) has approximately double the risk of death and hepatic decompensation than LS 25-49.9 kPa.

Early hepatic decompensation identifies patients with hepatocellular carcinoma treated with Atezolizumab plus Bevacizumab or Sorafenib at highest risk of death.

The prognosis of patients with unresectable hepatocellular carcinoma (uHCC) and compensated cirrhosis is influenced by cancer progression. Data on the incidence and the prognostic role of clinical hepatic decompensation following immune checkpoint inhibitor therapy are lacking. We aimed to assess whether early clinical hepatic decompensation (CHD) within 3 months from commencement of systemic therapy affects overall survival (OS) of patients treated with Atezolizumab plus Bevacizumab or Sorafenib. Individual patient data from IMbrave150 trial were analyzed. Cumulative incidence of CHD was assessed by competing risks analysis against HCC radiological progression. Early CHD and HCC radiological progression were assessed as predictors of OS by time-dependent Cox model. The 3- and 12-month rates of CHD were 7% and 12%, respectively, while the 3- and 12-month rates of HCC radiological progression were 23% and 52%. Albumin-bilirubin(ALBI)grade 2 (Sub-distribution hazard ratio[sHR] 1.79, 95%CI 1.01-3.19, p=0.049), INR(sHR 1.97, 95%CI 1.64-2.37, p<0.001) and presence of neoplastic macrovascular invasion (sHR 2.01, 95%CI 1.14-3.54, p=0.020) were independently associated with higher risk of CHD. Early CHD(HR 7.56, 95%CI 4.47-12.8) and early HCC radiological progression(HR 5.92, 95%CI 4.03-8.69), as first events, were independently associated with higher mortality. This study provides robust evidence that early CHD is associated with the highest risk of death in patients with uHCC undergoing systemic treatment. Within well-compensated participants, ALBI, INR and macrovascular invasion identify a population at higher risk of decompensation. Inclusion of clinical decompensation events in future prospective clinical trials may improve characterization of OS from systemic therapy of HCC.

HLA evolutionary divergence effect on bacterial infection risk in cirrhotic liver transplant candidates

Bacterial infections are common in cirrhosis patients, increasing the risk of decompensation and death. The impact of HLA evolutionary divergence (HED) on infection risk hasn't been studied in humans before. We conducted a retrospective study on cirrhosis patients awaiting liver transplantation (LT) from January 2019 to February 2022, examining class I and II-HED effects on bacterial infections and cirrhosis decompensation.We included 269 cirrhosis patients. Among them, 98 experienced 153 bacterial infections. Multivariable analysis after variable selection revealed that higher class II-HED was linked to fewer bacterial infections (p = 0.034), while class I-HED showed no effect (p = 0.074). Independent risk factors for bacterial infections included invasive procedures (p < 0.001), ICU hospitalization (p < 0.001), recent antibiotic treatment (p = 0.046), rifaximin use (p = 0.043), and cirrhosis decompensation (p = 0.002). Neither class I nor II-HED affected decompensation risk.This pioneering study shows that high class II-HED levels may protect against bacterial infections in cirrhosis patients awaiting LT, suggesting an immunological mechanism at play.

Top-Down Proteomics Identifies Plasma Proteoform Signatures of Liver Cirrhosis Progression

Cirrhosis, advanced liver disease, affects 2 to 5 million Americans. While most patients have compensated cirrhosis and may be fairly asymptomatic, many decompensate and experience life-threatening complications such as gastrointestinal bleeding, confusion (hepatic encephalopathy), and ascites, reducing life expectancy from 12 to less than 2years. Among patients with compensated cirrhosis, identifying patients at high risk of decompensation is critical to optimize care and reduce morbidity and mortality. Therefore, it is important to preferentially direct them towards specialty care which cannot be provided to all patients with cirrhosis. We used discovery top-down proteomics to identify differentially expressed proteoforms (DEPs) in the plasma of patients with progressive stages of liver cirrhosis with the ultimate goal to identify candidate biomarkers of disease progression. In this pilot study, we identified 209 DEPs across three stages of cirrhosis (compensated, compensated with portal hypertension, and decompensated), of which 115 derived from proteins enriched in the liver at a transcriptional level and discriminated the three stages of cirrhosis. Enrichment analyses demonstrated DEPs are involved in several metabolic and immunological processes known to be impacted by cirrhosis progression. We have preliminarily defined the plasma proteoform signatures of cirrhosis patients, setting the stage for ongoing discovery and validation of biomarkers for early diagnosis, risk stratification, and disease monitoring.

Prognostic impact of age on outcomes of hepatic decompensation in patients with compensated cirrhosis (CHESS2102): an international, multicenter cohort study.

Baveno VII criteria (B7C) and Baveno VI criteria (B6C) have been widely used to estimate the risk of hepatic decompensation. However, the impact of age on these criteria warrants further investigation. The international, multicenter cohort study included 1138 patients with compensated cirrhosis (median follow-up of 40.6 months), aiming to evaluate the value of age in predicting hepatic decompensation. We identified age as an independent predictor of hepatic decompensation, with 60 years determined as the optimal cut-off value. The occurrence of decompensation was 18.7% and 6.7% in the older (age ≥60 years) and younger (age <60 years) groups, respectively (p<0.001). We subsequently integrated age into the existing Baveno criteria. In patients not meeting Baveno criteria (defined as not meeting B6C or B7C), the older group exhibited a significantly elevated risk of decompensation compared to the younger group (p<0.05). However, no significant difference was observed between the older and younger groups in patients meeting Baveno criteria (p>0.05). In conclusion, our study demonstrated that integrating age into the Baveno criteria could enhance the assessment of hepatic decompensation. Age should be considered before discharging patients with compensated cirrhosis from the surveillance of hepatic decompensation.

Optimizing and Sustaining Clinical Outcomes in 88 US Hospitals Post-pandemic: A Quality Improvement Initiative

Optimizing outcomes of hospitalized patients anchors on standardizing processes in medical management, interventions to reduce the risk of decompensation, and prompt intervention when a patient decompensates. A quality improvement initiative (optimized sepsis and respiratory compromise management, reducing health care-associated infection and medication risk, swift management of the deteriorating patient, feedback on performance, and accountability) was implemented in a multistate health system. The primary outcome was risk-adjusted in-hospital mortality. Secondary outcomes included health care-associated infections, patient-days with hypoglycemic and severe hyperglycemic episodes, and hospital onset (HO) acute kidney injury (AKI). A total of 2,015,408 patients were admitted to 88 hospitals over the 36-month study period. Overall mortality improved from the baseline observed/expected (O/E) of 0.97 in 2021 to 0.74 in 2023 (-23.4%; 4,186 fewer deaths, p < 0.001). Controlling for baseline (2021) mortality O/E ratios, the mean mortality O/E ratio for 2023 was 0.74 for system and 0.84 for peers, representing a difference of -0.10 (p < 0.001, 95% confidence interval [CI] 0.12 - -0.07], with 1,807 fewer deaths). The standardized infection ratio declined for central line-associated blood stream infections by 24.8% (0.58; 88 fewer events), catheter-associated urinary tract infections by 30.6% (0.44; 98 fewer events), HO methicillin-resistant Staphylococcus aureus bacteremia by 29.0% (0.72; 67 fewer events), and HO Clostridioides difficile infection by 35.1% (0.36; 311 fewer events) in 2023 compared to 2021. HO AKI episodes dropped by 6.2% (8.6%; 1,725 fewer events), and patient-days with hypoglycemia and severe hyperglycemia decreased by 5.8% (4.0%; 4,840 fewer events) and 22.8% (5.2%; 30,065 fewer events), respectively. This systemwide initiative focusing on standardizing processes, feedback on performance, and accountability was associated with sustainable improvements in mortality and a reduction in infectious and safety events.

Hepatic Steatosis Estimated by VCTE-Derived CAP Scores Was Associated With Lower Risks of Liver-Related Events and All-Cause Mortality in Patients With Chronic Liver Diseases.

The controlled attenuated parameter (CAP) score derived from vibration-controlled transient elastography (VCTE, i.e., FibroScan) is a well-validated marker of hepatic steatosis. It is unclear whether CAP scores are associated with risks of liver-related outcomes or all-cause mortality. In this retrospective cohort study, we identified 7,587 United States veterans (2,689 with cured hepatitis C [hepatitis C virus], 1,523 with alcohol-associated liver disease, and 3,375 with metabolic dysfunction-associated steatotic liver disease [MASLD]) who underwent VCTE between May 2015 and December 2021. We followed patients for new hepatic decompensation, hepatocellular carcinoma, and death from the VCTE date until January 1, 2022. Multivariable Cox-proportional hazards regression was used to assess for the associations between CAP measurements and clinical outcomes, adjusting for age, sex, race/ethnicity, body mass index, Charlson Comorbidity Index, diabetes, liver disease etiology, liver stiffness measurements, and Fibrosis-4 score, and was reported separately by disease etiology and advanced fibrosis status. Over a median follow-up time of ∼1.9 years, hepatic steatosis (grades 1-3 vs 0) was associated with a lower risk of death (adjusted hazard ratio [aHR] 0.70, 95% CI: 0.57-0.85). Among patients with MASLD, hepatic steatosis was associated with a lower risk of decompensation (aHR 0.54, 95% CI: 0.32-0.90) and death (aHR 0.52, 95% CI: 0.37-0.73). These associations persisted in subgroup analyses of patients with advanced fibrosis and without cirrhosis. Among patients who underwent VCTE in clinical practice, the presence of substantial hepatic steatosis estimated by the CAP score was associated with lower all-cause mortality among all patients and lower risk of decompensation and death among those with MASLD.

Impact of non-selective beta blockers on further decompensation and death in decompensated cirrhosis: Benefit and risk stratification by MELD score.

Non-selective beta blockers (NSBBs) can reduce the risk of decompensation, but their impact on further decompensation has been rarely investigated. The aim is to evaluate the impact of NSBBs on further decompensation and death in decompensated cirrhosis stratified by the severity of liver disease. Overall, 332 decompensated cirrhotic patients were retrospectively included, of whom 149 used NSBBs. Kaplan-Meier and Nelson-Aalen cumulative risk curves as well as Cox regression and competing risk analyses were used to estimate the associations of NSBBs with further decompensation and death, if appropriate. Hazard ratio (HR) and sub-distribution HR (sHR) were calculated. Subgroup analyses were performed based on the model for end-stage liver disease (MELD) score at admission. In the overall analysis, the use of NSBBs was not significantly associated with further decompensation in multivariate competing risk analysis (sHR = 1.09, p = 0.580). In the subgroup analysis of patients with a MELD score of ≤9, the use of NSBBs was significantly associated with decreased risk of further decompensation in multivariate competing risk analysis (sHR = 0.57, p = 0.021). In the subgroup analysis of patients with a MELD score of >9, the use of NSBBs was associated with increased risk of further decompensation in multivariate competing risk analysis (sHR = 1.45, p = 0.044). Regardless of overall and subgroup analyses, the use of NSBBs was not significantly associated with death in multivariate Cox regression analyses. NSBBs may be beneficial for the prevention of further decompensation in cirrhotic patients with a MELD score of ≤9, but deleterious in those with a MELD score of >9.

Type 2 diabetes mellitus negatively affects the functional performance of 6-min step test in chronic heart failure: a 3-year follow-up study

BackgroundType 2 diabetes mellitus (T2DM) and chronic heart failure (CHF) present a decrease in functional capacity due to the intrinsic nature of both pathologies. It is not known about the potential impact of T2DM on functional capacity when assessed by 6-min step test (6MST) and its effect as a prognostic marker for fatal and non-fatal events in patients with CHF.Objectiveto evaluate the coexistence of T2DM and CHF in functional capacity through 6MST when compared to CHF non-T2DM, as well as to investigate the different cardiovascular responses to 6MST and the risk of mortality, decompensation of CHF and acute myocardial infarction (AMI) over 36 months.MethodsThis is a prospective cohort study with 36 months of follow-up in individuals with T2DM and CHF. All participants completed a clinical assessment, followed by pulmonary function testing, echocardiography, and 6MST. The 6MST was performed on a 20 cm high step and cardiovascular responses were collected: heart rate, systemic blood pressure, oxygen saturation, BORG dyspnea and fatigue. The risk of mortality, acute myocardial infarction and decompensation of CHF was evaluated.ResultsEighty-six participants were included. The CHF-T2DM group had a significantly lower functional capacity than the CHF non-T2DM group (p < 0.05). Forced Expiratory Volume in one second (L), ejection fraction (%), gender and T2DM influence and are predictors of functional capacity (p < 0.05; adjusted R squared: 0.419). CHF-T2DM group presented a higher risk of mortality and acute myocardial infarction over the 36 months of follow-up (p < 0.05), but not to the risk of decompensation (p > 0.05).ConclusionT2DM negatively affects the functional performance of 6MST in patients with CHF. Gender, ejection fraction (%), FEV1 (L) and T2DM itself negatively influence exercise performance.

Remote monitoring of cardiac implantable electronic devices to predict acute clinical decompensation events.

Heart failure (HF) patients are at constant risk of decompensation, and urgent hospital admissions can be life-threatening events. Monitoring biological variables has been proved to be an important mechanism to anticipate decompensations. TriageHF is a validated diagnostic algorithm tool available on Medtronic® cardiac implantable electronic devices that combines physiological data to stratify a patient's risk of HF hospitalization in the following 30 days in low, medium or high risk. We aimed to evaluate the utility of TriageHF algorithm to predict the occurrence of acute clinical decompensation events (ACDE), including HF and non-HF cardiovascular events, within a 30-day period in a population of HF patients with reduced ejection fraction. We reviewed the transmissions received by the Medtronic® Carelink™ Network between August 2022 and July 2023. The heart failure risk status (HFRS) and the device parameters contributing to that risk, from the previous 30 days, were collected, along with the occurrence of ACDEs within 30 days. We retrospectively assessed 207 transmissions from the 64 patients included in the study. Among the 93 medium HFRS transmissions, 16 (17.2%) resulted in ACDEs. For the 21 high HFRS transmissions, 10 (47.6%) resulted in ACDEs. Considering the ACDEs, 60.7% were preceded by an alarm-initiated transmission. Except for heart rate variability, each diagnostic parameter demonstrated effectiveness in stratifying risk for ACDEs. Optivol® and the Combined Heart Rhythm showed independent association with ACDEs (p<.001). Patients with medium and high HFRS were, respectively, 8.6 and 29.1 times more likely to experience an ACDE in the next 30 days than low risk patients. A medium-high HFRS conferred a sensitivity of 92.9% and a NPV of 97.8% for an ACDE. TriageHF is a useful method for predicting ACDEs and has the potential to trigger medical actions to prevent hospitalizations.

Immune Response and Risk of Decompensation following SARS-CoV-2 Infection in Outpatients with Advanced Chronic Liver Disease.

Advanced chronic liver disease (ACLD) is associated with a wide spectrum of immune dysfunction. The clinical impact of SARS-CoV-2 on the development of decompensation and immune response in unvaccinated outpatients has not as yet been clearly defined. This study aimed to evaluate the clinical and immunological impact of SARS-CoV-2 on outpatients with ACLD. This is an observational case-control study, in which ACLD outpatients were included prospectively and consecutively and classified into two groups: SARS-CoV-2 infected and non-infected. Patients' baseline characteristics and infection data were collected and analyzed. Immunoglobulin G (IgG) levels against Spike 1 were evaluated. The primary endpoint was risk of liver decompensation during follow-up, assessed after propensity score matching and adjusted by Cox regression. Between October 2020 and July 2021, ACLD outpatients (n = 580) were identified, and 174 patients with clinical follow-up were included. SARS-CoV-2 infection incidence was 7.6% (n = 44). Risk of liver decompensation was significantly higher after infection (HR = 2.43 [1.01-5.86], p = 0.048) vs. non-infection. The time of IgG evaluation was similar in all patients (n = 74); IgG concentrations were significantly higher in compensated vs. decompensated patients (1.02 ± 0.35 pg/mL vs. 0.34 ± 0.16 pg/mL, p < 0.0001) and correlated with hemoglobin levels. The dysregulation of the innate immune response in patients with decompensated liver disease increased the risk of further decompensation following SARS-CoV-2, mainly due to a worsening of ascites.

Hepatic decompensation is the major driver of mortality in patients with HCC treated with atezolizumab plus bevacizumab: The impact of successful antiviral treatment.

Unlike other malignancies, hepatic functional reserve competes with tumor progression in determining the risk of mortality from hepatocellular carcinoma (HCC). However, the relative contribution of hepatic decompensation over tumor progression in influencing overall survival (OS) has not been assessed in combination immunotherapy recipients. From the AB-real observational study (n = 898), we accrued 571 patients with advanced/unresectable hepatocellular carcinoma, Child-Pugh A class treated with frontline atezolizumab + bevacizumab (AB). Hepatic decompensation and tumor progression during follow-up were studied in relationship to patients' OS using a time-dependent Cox model. Baseline characteristics were evaluated as predictors of decompensation in competing risks analysis. During a median follow-up of 11.0 months (95% CI: 5.1-19.7), 293 patients (51.3%) developed tumor progression without decompensation, and 94 (16.5%) developed decompensation. In multivariable time-dependent analysis, decompensation (HR: 19.04, 95% CI: 9.75-37.19), hepatocellular carcinoma progression (HR: 9.91, 95% CI: 5.85-16.78), albumin-bilirubin (ALBI) grade 2/3 (HR: 2.16, 95% CI: 1.69-2.77), and number of nodules >3(HR: 1.63, 95% CI: 1.28-2.08) were independently associated with OS. Pretreatment ALBI grade 2/3 (subdistribution hazard ratio [sHR]: 3.35, 95% CI: 1.98-5.67) was independently associated with decompensation, whereas viral etiology was protective (sHR: 0.55, 95% CI: 0.34-0.87). Among patients with viral etiology, effective antiviral treatment was significantly associated with a lower risk of decompensation (sHR: 0.48, 95% CI: 0.25-0.93). Hepatic decompensation identifies patients with the worst prognosis following AB and is more common in patients with baseline ALBI >1 and nonviral etiology. Effective antiviral treatment may protect from decompensation, highlighting the prognostic disadvantage of patients with nonviral etiologies and the importance of multidisciplinary management to maximize OS.

Eligibility for vericiguat in a real-world, contemporary heart failure population.

Vericiguat is a soluble guanylate cyclase stimulator and improves survival in patients with heart failure (HF) with reduced ejection fraction (HFrEF) and an increased risk of decompensation. As real-world data on how many patients could be eligible for vericiguat therapy derive from outdated registries, we aimed to assess eligibility in a prospective cohort of patients with HF. Data from consecutive HF patients undergoing an elective ambulatory visit at five university hospitals from 3 July to 28 July 2023 were collected. Independent investigators assessed which patients (i) met the eligibility criteria of the VICTORIA trial, (ii) complied with HF guideline recommendations, (iii) met regulatory agency criteria, or (iv) met criteria for refundability according to the Italian regulatory agency. Patients (n=346, 72% men, median age 69years) had HFrEF in 57% of cases, left ventricular ejection fraction<45% in 68%, and New York Heart Association class II-IV symptoms in 76%. Patients meeting the eligibility criteria of the VICTORIA trial or European and American HF Guideline recommendations were 9% and 13%, respectively. Patients meeting Food and Drug Administration (FDA) or European Medicines Agency (EMA) label criteria were 19% and 17%, respectively. Drug costs would be covered by the Italian National Health System in 10% of patients [if a sodium-glucose cotransporter-2 inhibitor (SGLT2i) is not mandatory] or in 8% (if an SGLT2i is requested). In a real-world study, 9% of patients met the eligibility criteria of the VICTORIA trial, but up to 13% complied with guideline recommendations and up to 19% met FDA or EMA criteria. In Italy, drug costs would be covered by up to 10% of patients.

MAFLD in adults: non-invasive tests for diagnosis and monitoring of MAFLD.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the liver manifestation of a metabolic syndrome and is highly prevalent in the general population. There has been significant progress in non-invasive tests for MAFLD, from the diagnosis of fatty liver and monitoring of liver fat content in response to intervention, to evaluation of liver fibrosis and its change over time, and from risk stratification of patients within the context of clinical care pathways, to prognostication. Various non-invasive tests have also been developed to assess for fibrotic metabolic dysfunction-associated steatohepatitis, which has emerged as an important diagnostic goal, particularly in the context of clinical trials. Non-invasive tests can be used to diagnose clinically significant portal hypertension so that intervention can be administered to reduce the risk of decompensation. Furthermore, the use of risk stratification algorithms can identify at-risk patients for hepatocellular carcinoma surveillance. Beyond the liver, various tests that evaluate cardiovascular disease risk, assess sarcopenia and measure patient reported outcomes, can be utilized to improve the care of patients with MAFLD. This review provides an up-to-date overview of these non-invasive tests and the limitations of liver biopsy in the management of patients with MAFLD.

Top-Down Proteomics Identifies Plasma Proteoform Signatures of Liver Cirrhosis Progression.

Cirrhosis, advanced liver disease, affects 2-5 million Americans. While most patients have compensated cirrhosis and may be fairly asymptomatic, many decompensate and experience life-threatening complications such as gastrointestinal bleeding, confusion (hepatic encephalopathy), and ascites, reducing life expectancy from 12 to less than 2 years. Among patients with compensated cirrhosis, identifying patients at high risk of decompensation is critical to optimize care and reduce morbidity and mortality. Therefore, it is important to preferentially direct them towards specialty care which cannot be provided to all patients with cirrhosis. We used discovery Top-down Proteomics (TDP) to identify differentially expressed proteoforms (DEPs) in the plasma of patients with progressive stages of liver cirrhosis with the ultimate goal to identify candidate biomarkers of disease progression. In this pilot study, we identified 209 DEPs across three stages of cirrhosis (compensated, compensated with portal hypertension, and decompensated), of which 115 derived from proteins enriched in the liver at a transcriptional level and discriminated the three stages of cirrhosis. Enrichment analyses demonstrated DEPs are involved in several metabolic and immunological processes known to be impacted by cirrhosis progression. We have preliminarily defined the plasma proteoform signatures of cirrhosis patients, setting the stage for ongoing discovery and validation of biomarkers for early diagnosis, risk stratification, and disease monitoring.

Designing clinical trials to address alcohol use and alcohol-associated liver disease: an expert panel Consensus Statement.

Most patients with alcohol-associated liver disease (ALD) engage in heavy drinking defined as 4 or more drinks per day (56 g) or 8 (112 g) or more drinks per week for women and 5 or more drinks per day (70 g) or15 (210 g) or more drinks per week for men. Although abstinence from alcohol after diagnosis of ALD improves life expectancy and reduces the risk of decompensation of liver disease, few studies have evaluated whether treatment of alcohol use disorders will reduce progression of liver disease and improve liver-related outcomes. In November 2021, the National Institute of Alcohol Abuse and Alcoholism commissioned a task force that included hepatologists, addiction medicine specialists, statisticians, clinical trialists and members of regulatory agencies to develop recommendations for the design and conduct of clinical trials to evaluate the effect of alcohol use, particularly treatment to reduce or eliminate alcohol use in patients with ALD. The task force conducted extensive reviews of relevant literature on alcohol use disorders and ALD. Findings were presented at one in-person meeting and discussed over the next 16 months to develop the final recommendations. As few clinical trials directly address this topic, the 28 recommendations approved by all members of the task force represent a consensus of expert opinions.

TOP-072 Red blood cell distribution width-to-platelet ratio estimates the 3-year risk of decompensation in patients with metabolic dysfunction-associated steatotic liver disease-related cirrhosis

TOP-072 Red blood cell distribution width-to-platelet ratio estimates the 3-year risk of decompensation in patients with metabolic dysfunction-associated steatotic liver disease-related cirrhosis

Hepatic venous pressure gradient predicts risk of hepatic decompensation and liver-related mortality in patients with MASLD

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of advanced chronic liver disease (ACLD). Portal hypertension drives hepatic decompensation and is best diagnosed by hepatic venous pressure gradient (HVPG) measurement. Here, we investigate the prognostic value of HVPG in MASLD-related compensated ACLD (MASLD-cACLD). This European multicentre study included patients with MASLD-cACLD characterised by HVPG at baseline. Hepatic decompensation (variceal bleeding/ascites/hepatic encephalopathy) and liver-related mortality were considered the primary events of interest. A total of 340 patients with MASLD-cACLD (56.2% male; median age 62 [55-68] years, median MELD 8 [7-9], 71.2% with diabetes) were included. Clinically significant portal hypertension (CSPH: i.e., HVPG ≥10mmHg) was found in 209 patients (61.5%). During a median follow-up of 41.5 (27.5-65.8) months, 65 patients developed hepatic decompensation with a cumulative incidence of 10.0% after 2 years (2Y) and 30.7% after 5 years (5Y) in those with MASLD-cACLD with CSPH, compared to 2.4% after 2Y and 9.4% after 5Y in patients without CSPH. Variceal bleeding did not occur without CSPH. CSPH (subdistribution hazard ratio [SHR] 5.13; p <0.001) was associated with an increased decompensation risk and a higher HVPG remained an independent risk factor in the multivariable model (adjusted SHR per mmHg: 1.12, p <0.001). Liver-related mortality occurred in 37 patients at a cumulative incidence of 3.3% after 2Y and 21.4% after 5Y in CSPH. Without CSPH, the incidence after 5Y was 0.8%. Accordingly, a higher HVPG was also independently associated with a higher risk of liver-related death (adjusted SHR per mmHg: 1.20, p <0.001). HVPG measurement is of high prognostic value in MASLD-cACLD. In patients with MASLD-cACLD without CSPH, the short-term risk of decompensation is very low and liver-related mortality is rare, while the presence of CSPH substantially increases the risk of both. While the incidence of compensated advanced chronic liver disease (cACLD) due to metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing worldwide, insights into the impact of clinically significant portal hypertension (CSPH) on the risk of liver-related events in MASLD-cACLD remain limited. Based on the findings of this European multicentre study including 340 MASLD-cACLD patients, we could show that increasing HVPG values and the presence of CSPH in particular were associated with a significantly higher risk of first hepatic decompensation and liver-related mortality. In contrast, the short-term incidence of decompensation in patients with MASLD-cACLD without CSPH was low and the risk of liver-mortality remained negligible. Thus, HVPG measurements can provide important prognostic information for individualised risk stratification in MASLD-cACLD and may help facilitate the study of novel and promising treatment possibilities for MASLD.

Agreement Between Transthoracic Echocardiography and Computed Tomography Pulmonary Angiography for Detection of Right Ventricular Dysfunction in Pulmonary Embolism.

Right ventricular dysfunction (RVD) is the main determinant of mortality in patients with pulmonary embolism (PE). Thus, guidelines recommend the assessment of RVD with transthoracic echocardiography (TTE) or computed tomography pulmonary angiography (CTPA) among these patients. In this study, we investigated the agreement between TTE and CTPA for the detection of RVD. This single-center retrospective study included patients who were diagnosed with CTPA and underwent TTE within the first 24 hours following the diagnosis. Two hundred fifty-eight patients met the inclusion criteria. In 71.3% (184) of them, CTPA and TTE agreed on both the presence and absence of RVD. There was a moderate agreement between the 2 tests (Cohen's kappa = 0.404, P <.001). The agreement between right ventricle dysfunction on TTE and the increased right ventricle/left ventricle (RV/LV) on CTPA was fair (Cohen's kappa = 0.388, P <.001). Three patients died due to PE, and another 5 patients required urgent reperfusion therapy. Overall, adverse outcomes occurred in 4% (8) of patients. The sensitivity of modalities in the detection of adverse outcomes was 100%. Transthoracic echocardiography was more specific compared to CTPA (43% vs. 28%). Statistically, flattening/bulging of the interventricular septum on TTE was significantly associated with adverse outcomes. No individual CTPA parameter was related to adverse outcomes. Both CTPA and TTE are reliable imaging modalities in the detection of RVD. However, TTE is more specific, and this may help in the identification and appropriate management of patients at higher risk of decompensation. A combination of CTPA parameters rather than individual RV/LV ratios increases the sensitivity of CTPA.