Metabolic dysfunction-associated steatotic liver disease: Update and impact of new nomenclature on the American Association for the Study of Liver Diseases practice guidance on nonalcoholic fatty liver disease.

This commentary discusses how clinicians and various stakeholders can utilize the recently published American Association for the Study of Liver Diseases nonalcoholic fatty liver disease (AASLD NAFLD) Practice Guidance in light of the change in the nomenclature to steatotic liver disease and its subcategories. The new terminologies explained in this commentary make it easier for the readers to interchangeably use metabolic dysfunction-associated steatotic liver disease (MASLD) in place of NAFLD and metabolic-dysfunction associated steatohepatitis (MASH) instead of nonalcoholic steatohepatitis (NASH), respectively, as they read the NAFLD Practice Guidance. The guidance document is relevant and can be utilized for the diagnosis, risk stratification, and management of patients with MASLD. This commentary serves as an accompanying article to the NAFLD Practice Guidance and helps it clinical application in the light of the new nomenclature.

Quality measures in pre-liver transplant care by the Practice Metrics Committee of the American Association for the Study of Liver Diseases.

INTRODUCTION: The LT evaluation and waitlisting process is subject to variations in care that can impede quality. The American Association for the Study of Liver Diseases (AASLD) Practice Metrics Committee (PMC) developed quality measures and patient-reported experience measures (PREMs) along the continuum of pre-LT care to reduce care variation and guide patient-centered care. METHODS: Following a systematic literature review, candidate pre-LT measures were grouped into four phases of care: referral, evaluation and waitlisting, waitlist management, and organ acceptance. A modified Delphi panel with content expertise in hepatology, transplant surgery, psychiatry, transplant infectious disease, palliative care and social work selected the final set. Candidate PREMs spanned domains of cognitive health, emotional health, social well-being, and understanding the LT process. RESULTS: Of the 71 candidate measures, 41 were selected: 9 for referral; 20 for evaluation and waitlisting; 7 for waitlist management; and 5 for organ acceptance. A total of 14 were related to structure, 17 were process measures and 10 were outcome measures that focused on elements not typically measured in routine care. Among the PREMs, LT candidates rated items from understanding the LT process domain as the most important. CONCLUSION: The proposed pre-LT measures provide a framework for quality improvement and care standardization among LT candidates. Select measures apply to various stakeholders such as referring practitioners in the community and LT centers. Clinically meaningful measures that are distinct from those used for regulatory transplant reporting may facilitate local QI initiatives to improve access and quality of care.

The future of International Classification of Diseases coding in steatotic liver disease: An expert panel Delphi consensus statement.

BACKGROUND: Following the adoption of new nomenclature for steatotic liver disease, we aimed to build consensus on the use of International Classification of Diseases codes and recommendations for future research and advocacy. METHODS: Through a two-stage Delphi process, a core group (n = 20) reviewed draft statements and recommendations (n = 6), indicating levels of agreement. Following revisions, this process was repeated with a large expert panel (n = 243) from 73 countries. RESULTS: Consensus ranged from 88.8% to 96.9% (mean = 92.3%). CONCLUSIONS: This global consensus statement provides guidance on harmonizing the International Classification of Diseases coding for steatotic liver disease and future directions to advance the field.

Serum biomarker signature is predictive of the risk of hepatocellular cancer in patients with cirrhosis.

BACKGROUND: Inflammatory and metabolic biomarkers have been associated with hepatocellular cancer (HCC) risk in phases I and II biomarker studies. We developed and internally validated a robust metabolic biomarker panel predictive of HCC in a longitudinal phase III study. METHODS: We used data and banked serum from a prospective cohort of 2266 adult patients with cirrhosis who were followed until the development of HCC (n=126). We custom designed a FirePlex immunoassay to measure baseline serum levels of 39 biomarkers and established a set of biomarkers with the highest discriminatory ability for HCC. We performed bootstrapping to evaluate the predictive performance using C-index and time-dependent area under the receiver operating characteristic curve (AUROC). We quantified the incremental predictive value of the biomarker panel when added to previously validated clinical models. RESULTS: We identified a nine-biomarker panel (P9) with a C-index of 0.67 (95% CI 0.66 to 0.67), including insulin growth factor-1, interleukin-10, transforming growth factor ß1, adipsin, fetuin-A, interleukin-1 ß, macrophage stimulating protein α chain, serum amyloid A and TNF-α. Adding P9 to our clinical model with 10 factors including AFP improved AUROC at 1 and 2 years by 4.8% and 2.7%, respectively. Adding P9 to aMAP score improved AUROC at 1 and 2 years by 14.2% and 7.6%, respectively. Adding AFP L-3 or DCP did not change the predictive ability of the P9 model. CONCLUSIONS: We identified a panel of nine serum biomarkers that is independently associated with developing HCC in cirrhosis and that improved the predictive ability of risk stratification models containing clinical factors.

Rates, patterns, and predictors of specialty palliative care consultation among patients with acute-on-chronic liver failure.

Background & Aims: There is growing acceptance that principles of palliative care should be integrated into the management of serious illnesses affecting the liver, such as acute-on-chronic liver failure (ACLF). However, rates, patterns, and predictors of specialty palliative care consultation among patients with ACLF have not been well-described. Methods: We performed a retrospective cohort study of patients hospitalized with ACLF between 1/1/2008 and 12/31/2018 using the VOCAL cohort. Patients were followed until 6/2021. We used mixed-effects regression analyses to identify significant patient and facility factors associated with palliative care consultation. We examined timing of consultation, the influence of ACLF characteristics, and facility-level variation on receipt of palliative care consultation. Results: We identified 21,987 patients hospitalized with ACLF, of whom 30.5% received specialty palliative care consultation. Higher ACLF grade (ACLF-2 [odds ratio (OR) 1.82, 95% CI 1.67-1.99], ACLF-3 [OR 3.06, 95% CI 2.76-3.40]), prior specialty palliative care consultation (OR 2.62, 95% CI 2.36-2.91), and hepatocellular carcinoma (OR 2.10, 95% CI 1.89-2.33) were associated with consultation. Consultation occurred latest and closest to the time of death for patients with ACLF-3 compared to ACLF-1 and ACLF-2. Significant facility-level variation in consultation persisted among patients with ACLF-3, despite adjusting for multiple patient and facility factors. Conclusion: In this large cohort of hospitalized patients with ACLF, specialty palliative care consultation was rare, more common in patients with higher grade ACLF, and tended to occur closer to the time of death for the sickest patients. Greater attention should be placed on earlier integration of palliative care during acute hospitalizations in patients with ACLF. Impact and implications: Though palliative care consultation is recommended for patients with acute-on-chronic liver failure, there is no data demonstrating how often this occurs during hospitalizations, on a population level. We found that consultation occurs in only 30.5% of patients and occurs later for patients with grade 3 acute-on-chronic liver failure. Our data should provoke clinicians to urgently consider quality improvement efforts to integrate palliative care into the management of these seriously ill patients.

The Impact of Race on Pancreatic Cancer Treatment and Survival in the Nationwide Veterans Affairs Healthcare System.

OBJECTIVES: Among patients with pancreatic cancer, studies show racial disparities at multiple steps of the cancer care pathway. Access to healthcare is a frequently cited cause of these disparities. It remains unclear if racial disparities exist in an integrated, equal access public system such as the Veterans Affairs healthcare system. METHODS: We identified all patients diagnosed with pancreatic adenocarcinoma in the national Veterans Affairs Central Cancer Registry from January 2010 to December 2018. We examined the independent association between race and 3 endpoints: stage at diagnosis, receipt of treatment, and survival while adjusting for sociodemographic factors and medical comorbidities. RESULTS: We identified 8529 patients with pancreatic adenocarcinoma, of whom 79.5% were White and 20.5% were Black. Black patients were 19% more likely to have late-stage disease and 25% less likely to undergo surgical resection. Black patients had 13% higher mortality risk compared with White patients after adjusting for sociodemographic characteristics and medical comorbidities. This difference in mortality was no longer statistically significant after additionally adjusting for cancer stage and receipt of potentially curative treatment. CONCLUSIONS: Equal access to healthcare might have reduced but failed to eliminate disparities. Dedicated efforts are needed to understand reasons underlying these disparities in an attempt to close these persistent gaps.

A multisociety Delphi consensus statement on new fatty liver disease nomenclature.

The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favor of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panelists from 56 countries participated in 4 online surveys and 2 hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83%, and 78%, respectively. Seventy-four percent of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms "nonalcoholic" and "fatty" were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease. There was consensus to change the definition to include the presence of at least 1 of 5 cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic steatotic liver disease. A new category, outside pure metabolic dysfunction-associated steatotic liver disease, termed metabolic and alcohol related/associated liver disease (MetALD), was selected to describe those with metabolic dysfunction-associated steatotic liver disease, who consume greater amounts of alcohol per week (140-350 g/wk and 210-420 g/wk for females and males, respectively). The new nomenclature and diagnostic criteria are widely supported and nonstigmatising, and can improve awareness and patient identification.

Hepatocellular Carcinoma Incidence Threshold for Surveillance in Virologically Cured Hepatitis C Individuals.

BACKGROUND & AIMS: Guidelines recommend biannual surveillance for hepatocellular carcinoma (HCC) in hepatitis C individuals with cirrhosis if the HCC incidence rate is above 1.5 per 100 person-years (PY). However, the incidence threshold for surveillance in individuals who achieve a virologic cure is unknown. We estimated the HCC incidence rate above which routine HCC surveillance is cost-effective in this growing population of virologically cured hepatitis C individuals with cirrhosis or advanced fibrosis. METHODS: We developed a Markov-based microsimulation model of the natural history of HCC in individuals with hepatitis C who achieved virologic cure with oral direct-acting antivirals. We used published data on the natural history of hepatitis C, competing risk post virologic cure, HCC tumor progression, real-world HCC surveillance adherence, contemporary HCC treatment options and associated costs, and utilities of different health states. We estimated the HCC incidence above which biannual HCC surveillance using ultrasound and alpha-fetoprotein would be cost-effective. RESULTS: In virologically cured hepatitis C individuals with cirrhosis or advanced fibrosis, HCC surveillance is cost-effective if HCC incidence exceeds 0.7 per 100 PY using $100,000 per quality-adjusted life year willingness-to-pay. At this HCC incidence, routine HCC surveillance would result in 2650 and 5700 additional life years per 100,000 cirrhosis and advanced fibrosis persons, respectively, compared with no surveillance. At $150,000 willingness-to-pay, surveillance is cost-effective if HCC incidence exceeds 0.4 per 100 PY. Sensitivity analysis showed that the threshold mostly remained below 1.5 per 100 PY. CONCLUSIONS: The contemporary HCC incidence threshold is much lower than the previous 1.5% incidence value used to guide HCC surveillance decisions. Updating clinical guidelines could improve the early diagnosis of HCC.

Emergency Presentations Predict Worse Outcomes Among Patients with Pancreatic Cancer.

BACKGROUND: Emergency presentation (EP) of cancer, a new cancer diagnosis made following an emergency department (ED) visit, is associated with worse patient outcomes and greater organizational stress on healthcare systems. Pancreatic cancer has the highest rate of EPs among European studies but remains understudied in the U.S. AIMS: To evaluate the association between pancreatic cancer EPs and cancer stage, treatment, and survival. METHODS: We conducted a retrospective cohort study among patients with pancreatic adenocarcinoma diagnosed from 2007 to 2019 at a tertiary-care Veterans Affairs medical center. Electronic health records were reviewed to identify EP cases, defined as a new pancreatic cancer diagnosis made within 30 days of an ED visit where cancer was suspected. We used multivariate logistic regression models and Cox proportional hazards models to examine the associations between EPs and cancer stage, treatment, and survival. RESULTS: Of 243 pancreatic cancer patients, 66.7% had EPs. There was no difference in stage by EP status. However, patients diagnosed through EPs were 72% less likely to receive cancer treatment compared to non-emergency presenters (adjusted OR 0.28; 95% CI 0.13-0.57). Patients with EPs also had a 73% higher mortality risk (adjusted HR 1.73; 95% CI 1.29-2.34). This difference in mortality remained statistically significant after adjusting for cancer stage and receipt of cancer treatment (adjusted HR 1.47; 95% CI 1.09-1.99). CONCLUSIONS: Pancreatic cancer EPs are common and independently associated with lower treatment rates and survival. Enhanced understanding of process breakdowns that lead to EPs can help identify care gaps and inform future quality improvement efforts.

Global trends in hepatocellular carcinoma epidemiology: implications for screening, prevention and therapy.

Hepatocellular carcinoma (HCC) mortality rates are increasing globally, and particularly in the Western world. Cirrhosis remains the predominant risk factor for HCC. However, epidemiological shifts in the incidence of HCC from patients with virus-related liver disease to those with non-viral aetiologies, including alcohol-associated and metabolic dysfunction-associated steatotic liver disease, have important implications for prevention, surveillance and treatment. Hepatitis B vaccination and antiviral therapy for hepatitis B and C are effective for primary prevention of virus-related HCCs, but chemoprevention strategies for non-viral liver disease remain an unmet need. Emerging data suggest associations between aspirin, statins, metformin and coffee and reduced HCC incidence, although none has been proved to be causally related. Secondary prevention of HCC via semi-annual surveillance is associated with improvements in early detection and thus reduced mortality; however, current tools, including abdominal ultrasonography, have suboptimal sensitivity for the detection of early stage HCC, particularly in patients with obesity and/or non-viral liver disease. Promising blood-based or imaging-based surveillance strategies are emerging, although these approaches require further validation before adoption in clinical practice. In the interim, efforts should be focused on maximizing use of the existing surveillance tools given their prevalent underuse globally. Remarkable advances have been made in the treatment of HCC, including expanded eligibility for surgical therapies, improved patient selection for locoregional treatments and increased systemic treatment options, including immune-checkpoint inhibitors. In this Review, we discuss trends in the epidemiology of HCC and their implications for screening, prevention and therapy.

Bioimpedance analysis predicts the etiology of cirrhosis in a prospective cohort study.

BACKGROUND: Obesity is associated with an increased risk of developing cirrhosis. However, body mass index (BMI) and waist-to-hip ratio (WHR) may not be indicative of body composition parameters that predispose to cirrhosis. Bioimpedance analysis (BIA) is a noninvasive cost-efficient method for more detailed estimation of body composition. METHODS: We examined patients with cirrhosis who underwent BIA as part of enrollment into a prospective cohort study. We examined the correlation between BIA variables, BMI, and WHR. We performed sex-adjusted and race-adjusted and race-specific multivariable logistic regression analyses to examine the association between anthropometric variables and risk factors [NAFLD, alcohol-associated liver disease (ALD), and HCV]. RESULTS: We analyzed data from 348 cirrhosis patients; 23.3% were women; 48.3% were non-Hispanic White; 19.3% were Hispanic; and 30.7% were African American. The cirrhosis etiology was 21.8% NAFLD, 56.9% HCV mostly cured, and 11.5% ALD. Several BIA variables correlated well with BMI, and others showed modest correlations, but none correlated well with WHR. Higher body fat mass and basal metabolic rate were positively associated, while higher lean body mass, dry lean mass, total body water, or skeletal muscle mass were negatively associated with NAFLD. Associations between these BIA parameters and ALD-related cirrhosis were in the opposite direction. These associations of BIA variables were seen only in Hispanic and non-Hispanic White patients but not non-Hispanic Blacks. BIA variables were more predictive of cirrhosis etiology than BMI or WHR. CONCLUSIONS: Among patients with cirrhosis, several BIA-derived measurements indicative of body fat and muscle are associated with NAFLD and ALD etiology. BIA variables show stronger associations, as well as race/ethnicity-specific associations, with cirrhosis etiology than those of BMI or WHR.

A Study of Dietary Patterns Derived by Cluster Analysis and Their Association With Metabolic Dysfunction-Associated Steatotic Liver Disease Severity Among Hispanic Patients.

INTRODUCTION: Diet is a modifiable metabolic dysfunction-associated steatotic liver disease (MASLD) risk factor, but few studies have been conducted among Hispanic patients, despite the fact that MASLD prevalence and severity are highest among this ethnic subgroup. We aimed to identify prevalent dietary patterns among Hispanic patients using cluster analysis and to investigate associations with MASLD severity. METHODS: This cross-sectional analysis included 421 Harris County MASLD Cohort participants who self-reported Hispanic ethnicity and completed baseline food frequency questionnaires. All included patients had MASLD, diagnosed per standard clinical criteria. K-means analysis was used to identify clusters of patients sharing similar dietary habits. Multivariable adjusted logistic regression was used to estimate associations of dietary clusters with aminotransferases among the overall sample and with histologic steatosis, metabolic dysfunction-associated steatohepatitis, and fibrosis among a subsample of patients who underwent liver biopsy within 6 months of their baseline food frequency questionnaire (n = 186). RESULTS: We identified 2 clusters: a plant-food/prudent and a fast-food/meat pattern. The fast-food/meat pattern was associated with 2.47-fold increased odds (95% confidence interval 1.31-4.65) of more severe steatosis than the plant-food/prudent pattern after adjusting for demographics, metabolic score, physical activity, and alcohol ( q = 0.0159). No significant association was observed between diet and aminotransferases, metabolic dysfunction-associated steatohepatitis, or fibrosis. DISCUSSION: Given the importance of sociocultural influences on diet, it is important to understand dietary patterns prevalent among Hispanic patients with MASLD. Using cluster analysis, we identified 1 plant-based pattern vs 1 distinct fast-food/meat-based pattern associated with detrimental effects among our population. This information is an important starting point for tailoring dietary interventions for Hispanic patients with MASLD.

Behavioral weight-loss interventions for patients with NAFLD: A systematic scoping review.

BACKGROUND: Clinically significant weight loss-which requires sustained dietary and physical activity changes-is central to treating NAFLD. Although behavioral interventions have demonstrated effectiveness in promoting weight loss among primary prevention populations, the data are limited among patients with NAFLD who need weight loss for treatment. We undertook this scoping review to map the existing data on the characteristics, weight-loss outcomes, and determinants of success of interventions evaluated among patients with NAFLD. METHODS: We searched Medline, EMBASE, Cochrane, PsycINFO, and Web of Science from inception to January 1, 2023 to identify publications reporting weight loss among adults with NAFLD in behavioral weight-loss interventions. We summarized interventions and classified them as successful if there was an average weight loss of ≥ 5% from baseline across enrolled participants or achieved by ≥ 50% of enrolled participants. RESULTS: We included 28 studies: 10 randomized control trials, ten quasi-experimental, and 8 observational studies. Intervention delivery, duration, and counseling frequency varied; 12 were successful. Retention was highest among telephone interventions and lowest among "real-world" face-to-face interventions. Patients who were women, younger, and/or had multiple metabolic conditions were most likely to dropout. Successful interventions had biweekly counseling, specific physical activity, and calorie targets, behavioral theory grounding, and promoted goal-setting, self-monitoring, and problem-solving. CONCLUSION: There are limited data on behavioral weight-loss interventions in NAFLD. Research is needed to develop effective interventions generalizable to diverse patient populations and that maximize adherence, particularly among patients who are diabetic, women, and younger.

Hepatocellular carcinoma surveillance - utilization, barriers and the impact of changing aetiology.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. Surveillance for HCC is critical for early detection and treatment, but fewer than one-quarter of individuals at risk of HCC undergo surveillance. Multiple failures across the screening process contribute to the underutilization of surveillance, including limited disease awareness among patients and health-care providers, knowledge gaps, and difficulty recognizing patients who are at risk. Non-alcoholic fatty liver disease and alcohol-associated liver disease are the fastest-rising causes of HCC-related death worldwide and are associated with unique barriers to surveillance. In particular, more than one-third of patients with HCC related to non-alcoholic fatty liver disease do not have cirrhosis and therefore lack a routine indication for HCC surveillance on the basis of current practice guidelines. Semi-annual abdominal ultrasound with measurement of α-fetoprotein levels is recommended for HCC surveillance, but the sensitivity of this approach for early HCC is limited, especially for patients with cirrhosis or obesity. In this Review, we discuss the current status of HCC surveillance and the remaining challenges, including the changing aetiology of liver disease. We also discuss strategies to improve the utilization and quality of surveillance for HCC.

Cost of Care for Patients With Cirrhosis.

INTRODUCTION: There are limited longitudinal data on the cost of treating patients with cirrhosis, which hampers value-based improvement initiatives. METHODS: We conducted a retrospective cohort study of patients with cirrhosis seen in the Veterans Affairs health care system from 2011 to 2015. Patients were followed up through 2019. We identified a sex-matched and age-matched control cohort without cirrhosis. We estimated incremental annual health care costs attributable to cirrhosis for 4 years overall and in subgroups based on severity (compensated, decompensated), cirrhosis complications (ascites, encephalopathy, varices, hepatocellular cancer, acute kidney injury), and comorbidity (Deyo index). RESULTS: We compared 39,361 patients with cirrhosis with 138,964 controls. The incremental adjusted costs for caring of patients with cirrhosis were $35,029 (95% confidence interval $32,473-$37,585) during the first year and ranged from $14,216 to $17,629 in the subsequent 3 years. Cirrhosis complications accounted for most of these costs. Costs of managing patients with hepatic encephalopathy (year 1 cost, $50,080) or ascites ($50,364) were higher than the costs of managing patients with varices ($20,488) or hepatocellular cancer ($37,639) in the first year. Patients with acute kidney injury or those who had multimorbidity were the most costly at $64,413 and $66,653 in the first year, respectively. DISCUSSION: Patients with cirrhosis had substantially higher health care costs than matched controls and multimorbid patients had even higher costs. Cirrhosis complications accounted for most of the excess cost, so preventing complications has the largest potential for cost saving and could serve as targets for improvement.

Diabetes Status and Pancreatic Cancer Survival in the Nationwide Veterans Affairs Healthcare System.

BACKGROUND: Long-standing type 2 diabetes is a known risk factor for developing pancreatic cancer, however, its influence on cancer-associated outcomes is understudied. AIMS: To examine the associations between diabetes status and pancreatic cancer outcomes. METHODS: We identified patients diagnosed with pancreatic adenocarcinoma in the national Veterans Administration System from 2010 to 2018. We classified each patient by pre-cancer diagnosis diabetes status: no diabetes, new-onset diabetes (NOD) of ≤ 3 years duration, or long-standing diabetes of > 3 years duration. We used Cox proportional hazards models to examine the association between diabetes status and survival. We adjusted the models for age, race, sex, body mass index, tobacco, and alcohol use, coronary artery disease, hypertension, chronic kidney disease, year of cancer diagnosis, and cancer stage and treatment. RESULTS: We identified 6342 patients diagnosed with pancreatic adenocarcinoma. Most had long-standing diabetes (45.7%) prior to their cancer diagnosis, 14.5% had NOD, and 39.8% had no diabetes. Patients with long-standing diabetes had 10% higher mortality risk compared to patients without diabetes after adjusting for sociodemographic factors and medical comorbidities (adjusted HR 1.10; 95% CI 1.03-1.16). This difference in mortality remained statistically significant after additionally adjusting for cancer stage and receipt of potentially curative treatment (adjusted HR 1.09; 95% CI 1.02-1.15). There was no significant difference in mortality between patients with NOD compared to those without diabetes. CONCLUSIONS: Long-standing but not new-onset diabetes is independently associated with increased mortality among patients with pancreatic cancer. This information has implication for prognostication and risk stratification among pancreatic cancer patients.

Targets and study design for symptom-focused trials aimed at patients with cirrhosis: An expert consensus.

BACKGROUND: Symptom-focused trials are critically needed for patients with cirrhosis. However, this work would benefit from standard processes and validated measures. METHODS: A writing group was formed among hepatologists, nurses, palliative care providers, pharmacists, and clinical trial experts focused on symptom management in patients with cirrhosis to define the key (1) components of trial design, (2) symptom targets, (3) measurement, and (4) outcomes for each target. From July 2022 to January 2023, panelists participated in an iterative process of developing and arriving at a consensus for each component. The goal was to provide consensus definitions that can be operationalized in future clinical trials, including for patients with cirrhosis. RESULTS: The panel reached a consensus on key reporting features for clinical trials, along with considerations for study design. Nine key symptom targets (muscle cramps, pruritus, pain, fatigue, sexual dysfunction, sleep disorders, depression and anxiety, nausea/vomiting, and dyspnea/breathlessness) were identified. The panel selected instruments that can be considered for clinical trials based on psychometric validation and previous experience. The panel identified ongoing needs, including instrument validation, safety data, evidence about non-pharmacologic interventions, and comparative effectiveness studies. CONCLUSION: This expert panel identified key design, reporting, and measurement elements to standardize processes and measures in future symptom-focused clinical trials in the context of cirrhosis.

Risk Stratification Model for Hepatocellular Cancer in Patients With Cirrhosis.

BACKGROUND & AIMS: The available risk stratification indices for hepatocellular cancer (HCC) have limited applicability. We developed and externally validated an HCC risk stratification index in U.S. cohorts of patients with cirrhosis. METHODS: We used data from 2 prospective U.S. cohorts to develop the risk index. Patients with cirrhosis were enrolled from 8 centers and followed until development of HCC, death, or December 31, 2021. We identified an optimal set of predictors with the highest discriminatory ability (C-index) for HCC. The predictors were refit using competing risk regression and its predictive performance was evaluated using the area under the receiver-operating characteristic curve (AUROC). External validation was performed in a cohort of 21,550 patients with cirrhosis seen in the U.S Veterans Affairs system between 2018 and 2019 with follow-up through 2021. RESULTS: We developed the model in 2431 patients (mean age 60 years, 31% women, 24% cured hepatitis C, 16% alcoholic liver disease, and 29% nonalcoholic fatty liver disease). The selected model had a C-index of 0.77 (95% confidence interval [CI], 0.73-0.81), and the predictors were age, sex, smoking, alcohol use, body mass index, etiology, α-fetoprotein, albumin, alanine aminotransferase, and platelet levels. The AUROCs were 0.75 (95% CI, 0.65-0.85) at 1 year and 0.77 (95% CI, 0.71-0.83) at 2 years, and the model was well calibrated. In the external validation cohort, the AUROC at 2 years was 0.70 with excellent calibration. CONCLUSION: The risk index, including objective and routinely available risk factors, can differentiate patients with cirrhosis who will develop HCC and help guide discussions regarding HCC surveillance and prevention. Future studies are needed for additional external validation and refinement of risk stratification.