Preoperative Hepatology and Primary Care Visits Improve Postoperative Outcomes in Patients with Cirrhosis Undergoing Surgery.

BACKGROUND AND AIMS: Cirrhosis patients are at increased risk for postoperative complications. It remains unclear whether preoperative nonsurgical clinician visits improve postoperative outcomes. We assessed the impact of preoperative primary care physician (PCP) and/or Gastroenterologist/Hepatologist (GI/Hep) visits on postoperative mortality in cirrhosis patients undergoing surgery and explored differences in medication changes and paracentesis rates as potential mediators. METHODS: This was a retrospective cohort study of cirrhosis patients in the Veterans Health Administration who underwent surgery between 2008 and 2016. We compared 1982 patients with preoperative PCP and/or GI/Hep visits with 1846 propensity matched patients without preoperative visits. We used Cox regression and Fine and Gray competing risk regression to evaluate the association between preoperative visit type and postoperative mortality at 6 months. RESULTS: Patients with preoperative GI/Hep and PCP visits had a 45% lower hazard of postoperative mortality compared to those without preoperative visits (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.35-0.87). A smaller effect size was noted with GI/Hep preoperative visit alone (HR, 0.69; 95% CI, 0.48-0.99) or PCP visit alone (HR, 0.70; 95% CI, 0.53-0.93). Patients with preoperative PCP/GI/Hep visits were more likely to have diuretics, spontaneous bacterial peritonitis prophylaxis, and hepatic encephalopathy medications newly initiated and/or dose adjusted and more likely to receive preoperative paracentesis as compared to those without preoperative visits. CONCLUSION: Preoperative PCP/GI/Hep visits are associated with a reduced risk of postoperative mortality with the greatest risk reduction observed in those with both PCP and GI/Hep visits. This synergistic effect highlights the importance of a multidisciplinary approach in the preoperative care of cirrhosis patients.

Management of coagulopathy among patients with cirrhosis undergoing upper endoscopy and paracentesis: Persistent gaps and areas of consensus in a multispecialty Delphi.

Patients with cirrhosis have abnormal coagulation indices such as a high international normalized ratio and low platelet count, but these do not correlate well with periprocedural bleeding risk. We sought to develop a consensus among the multiple stakeholders in cirrhosis care to inform process measures that can help improve the quality of the periprocedural management of coagulopathy in cirrhosis. We identified candidate process measures for periprocedural coagulopathy management in multiple contexts relating to the performance of paracentesis and upper endoscopy. An 11-member panel with content expertise was convened. It included nominees from professional societies for interventional radiology, transfusion medicine, and anesthesia as well as representatives from hematology, emergency medicine, transplant surgery, and community practice. Each measure was evaluated for agreement using a modified Delphi approach (3 rounds of rating) to define the final set of measures. Out of 286 possible measures, 33 measures made the final set. International normalized ratio testing was not required for diagnostic or therapeutic paracentesis as well as diagnostic endoscopy. Plasma transfusion should be avoided for all paracenteses and diagnostic endoscopy. No consensus was achieved for these items in therapeutic intent or emergent endoscopy. The risks of prophylactic platelet transfusions exceed their benefits for outpatient diagnostic paracentesis and diagnostic endosopies. For the other procedures examined, the risks outweigh benefits when platelet count is >20,000/mm 3 . It is uncertain whether risks outweigh benefits below 20,000/mm 3 in other contexts. No consensus was achieved on whether it was permissible to continue or stop systemic anticoagulation. Continuous aspirin was permissible for each procedure. Clopidogrel was permissible for diagnostic and therapeutic paracentesis and diagnostic endoscopy. We found many areas of consensus that may serve as a foundation for a common set of practice metrics for the periprocedural management of coagulopathy in cirrhosis.

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

The liver transplantation (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 along the continuum of pre-LT care to reduce care variation and guide patient-centered care. Following a systematic literature review, candidate pre-LT measures were grouped into 4 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 patient-reported experience measures spanned domains of cognitive health, emotional health, social well-being, and understanding the LT process. 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 patient-reported experience measures, candidates of LT rated items from understanding the LT process domain as the most important. The proposed pre-LT measures provide a framework for quality improvement and care standardization among candidates of LT. 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 quality improvement initiatives to improve access and quality of care.

Association between public health policies on alcohol and worldwide cancer, liver disease and cardiovascular disease outcomes.

BACKGROUND & AIMS: The long-term impact of alcohol-related public health policies (PHPs) on disease burden is unclear. We aimed to assess the association between alcohol-related PHPs and alcohol-related health consequences. METHODS: We conducted an ecological multi-national study including 169 countries. We collected data on alcohol-related PHPs from the WHO Global Information System of Alcohol and Health 2010. Data on alcohol-related health consequences between 2010-2019 were obtained from the Global Burden of Disease database. We classified PHPs into five items, including criteria for low, moderate, and strong PHP establishment. We estimated an alcohol preparedness index (API) using multiple correspondence analysis (0 lowest and 100 highest establishment). We estimated an incidence rate ratio (IRR) for outcomes according to API using adjusted multilevel generalized linear models with a Poisson family distribution. RESULTS: The median API in the 169 countries was 54 [IQR 34.9-76.8]. The API was inversely associated with alcohol use disorder (AUD) prevalence (IRR 0.13; 95% CI 0.03-0.60; p = 0.010), alcohol-associated liver disease (ALD) mortality (IRR 0.14; 95% CI 0.03-0.79; p = 0.025), mortality due to neoplasms (IRR 0.09; 95% CI 0.02-0.40; p = 0.002), alcohol-attributable hepatocellular carcinoma (HCC) (IRR 0.13; 95% CI 0.02-0.65; p = 0.014), and cardiovascular diseases (IRR 0.09; 95% CI 0.02-0.41; p = 0.002). The highest associations were observed in the Americas, Africa, and Europe. These associations became stronger over time, and AUD prevalence was significantly lower after 2 years, while ALD mortality and alcohol-attributable HCC incidence decreased after 4 and 8 years from baseline API assessment, respectively (p <0.05). CONCLUSIONS: The API is a valuable instrument to quantify the robustness of alcohol-related PHP establishment. Lower AUD prevalence and lower mortality related to ALD, neoplasms, alcohol-attributable HCC, and cardiovascular diseases were observed in countries with a higher API. Our results encourage the development and strengthening of alcohol-related policies worldwide. IMPACT AND IMPLICATIONS: We first developed an alcohol preparedness index, an instrument to assess the existence of alcohol-related public policies for each country. We then evaluated the long-term association of the country's alcohol preparedness index in 2010 with the burden of chronic liver disease, hepatocellular carcinoma, other neoplasms, and cardiovascular disease. The strengthening of alcohol-related public health policies could impact long-term mortality rates from cardiovascular disease, neoplasms, and liver disease. These conditions are the main contributors to the global burden of disease related to alcohol use. Over time, this association has not only persisted but also grown stronger. Our results expand the preliminary evidence regarding the importance of public health policies in controlling alcohol-related health consequences.

Secondary Prevention of Esophageal Variceal Bleeding Is Often Imperfect: A National, Population-Based Cohort Study of 3592 Patients.

BACKGROUND AND AIMS: Secondary prevention of esophageal variceal bleeding is important to improve prognosis, but uptake of guidelines is unknown in a real-world setting. Here, we determined the proportion of patients receiving appropriate nonselective beta-blocker treatment and repeat upper endoscopy after a first episode of esophageal variceal bleeding within a reasonable time frame. METHODS: Population-based registers were used to identify all patients with a first episode of esophageal variceal bleeding in Sweden from 2006 to 2020. Crosslinkage between registers was performed to receive information on the cumulative incidence of patients with a dispensation of nonselective beta-blockers and repeat upper endoscopy within 120 days from baseline. Overall mortality was investigated using Cox regression. RESULTS: In total, 3592 patients were identified, with a median age of 63 (interquartile range, 54-71) years. The cumulative incidence of a dispensation of nonselective beta-blockers and a repeat endoscopy within 120 days was 33%. A total of 77% received either of these treatments. Overall mortality was high, with 65% of patients dying after esophageal variceal bleeding during the full follow-up period (median 1.7 years). We observed an improved overall mortality during the later years of the study period (adjusted hazard ratio for the 2016-2020 period compared with the 2006-2010 period, 0.80; 95% confidence interval, 0.71-0.89). Patients with receipt of nonselective beta-blockers and repeat upper endoscopy had better overall survival compared with those without (adjusted hazard ratio, 0.80; 95% confidence interval, 0.72-0.90). CONCLUSIONS: Secondary prevention of esophageal variceal bleeding has not been widely undertaken, with many patients not receiving guideline-supported interventions within a reasonable time frame. This highlights a need to raise awareness on appropriate prevention strategies to clinicians and patients.

Diagnosis and Management of Cirrhosis and Its Complications: A Review.

Importance: Cirrhosis affects approximately 2.2 million adults in the US. From 2010 to 2021, the annual age-adjusted mortality of cirrhosis increased from 14.9 per 100 000 to 21.9 per 100 000 people. Observations: The most common causes of cirrhosis in the US, which can overlap, include alcohol use disorder (approximately 45% of all cases of cirrhosis), nonalcoholic fatty liver disease (26%), and hepatitis C (41%). Patients with cirrhosis experience symptoms including muscle cramps (approximately 64% prevalence), pruritus (39%), poor-quality sleep (63%), and sexual dysfunction (53%). Cirrhosis can be diagnosed by liver biopsy but may also be diagnosed noninvasively. Elastography, a noninvasive assessment of liver stiffness measured in kilopascals, can typically confirm cirrhosis at levels of 15 kPa or greater. Approximately 40% of people with cirrhosis are diagnosed when they present with complications such as hepatic encephalopathy or ascites. The median survival time following onset of hepatic encephalopathy and ascites is 0.92 and 1.1 years, respectively. Among people with ascites, the annual incidence of spontaneous bacterial peritonitis is 11% and of hepatorenal syndrome is 8%; the latter is associated with a median survival of less than 2 weeks. Approximately 1% to 4% of patients with cirrhosis develop hepatocellular carcinoma each year, which is associated with a 5-year survival of approximately 20%. In a 3-year randomized clinical trial of 201 patients with portal hypertension, nonselective ß-blockers (carvedilol or propranolol) reduced the risk of decompensation or death compared with placebo (16% vs 27%). Compared with sequential initiation, combination aldosterone antagonist and loop diuretics were more likely to resolve ascites (76% vs 56%) with lower rates of hyperkalemia (4% vs 18%). In meta-analyses of randomized trials, lactulose was associated with reduced mortality relative to placebo (8.5% vs 14%) in randomized trials involving 705 patients and reduced risk of recurrent overt hepatic encephalopathy (25.5% vs 46.8%) in randomized trials involving 1415 patients. In a randomized clinical trial of 300 patients, terlipressin improved the rate of reversal of hepatorenal syndrome from 39% to 18%. Trials addressing symptoms of cirrhosis have demonstrated efficacy for hydroxyzine in improving sleep dysfunction, pickle brine and taurine for reducing muscle cramps, and tadalafil for improving sexual dysfunction in men. Conclusions and Relevance: Approximately 2.2 million US adults have cirrhosis. Many symptoms, such as muscle cramps, poor-quality sleep, pruritus, and sexual dysfunction, are common and treatable. First-line therapies include carvedilol or propranolol to prevent variceal bleeding, lactulose for hepatic encephalopathy, combination aldosterone antagonists and loop diuretics for ascites, and terlipressin for hepatorenal syndrome.

Medical malpractice claims in Hepatology: Rates, Reasons, and Results.

BACKGROUND: Clinicians are motivated to provide safe, high-quality care to patients with chronic liver disease. This includes the desire to avoid litigation. Data are limited regarding the actual sources of medicolegal risk in chronic liver disease. METHODS: We conducted a review of a national liability insurer (Candello) with an additional granular analysis of our institution's registry of liability claims. We included closed cases involving chronic liver disease-related encounters between 2012 and 2021. We determined rates of legal claims from a denominator of unique patients with cirrhosis or transplant care seen over the study period. RESULTS: Local database: We retrieved 39 claims of which 15 involved patients with non-cirrhotic chronic liver disease, 13 involved cirrhosis (0.06% incidence), and 11 involved patients who underwent transplantation (0.6% incidence). Most claims involved periprocedural complications. Others included adverse reactions to prophylactic plasma transfusion, medication-induced HE, and falls/fractures. NATIONAL DATABASE: We found 94 claims related to liver disease out of 102,575 (0.09%) total claims. Overall, 56% involved diagnosis-related issues (failure/delay in ordering a diagnostic test, failure to appreciate and reconcile a symptom/sign or result, or the misinterpretation of a diagnostic study). Miscommunication between providers and between providers and patients was implicated in 22% of cases. Patient behavior-related factors (nonadherence with scheduled appointments, treatments, or diagnostic testing) factored in 20% of cases. Selection or the management of therapy played a role in 7% of cases. Very rarely were cases associated with technical skill (4%), house staff supervision (3%), or weekend/holiday care (1%). Fifty-one (55%) claims involved HCC. CONCLUSION: We provide the rates and reasons for medical malpractice claims in hepatology.

Food Insecurity Is Associated With Chronic Liver Disease Among US Adults.

BACKGROUND: Food insecurity is associated with many poor health outcomes. Most contemporary liver disease is metabolic and impacted by nutritional status. Data regarding the association between food insecurity and chronic liver disease are limited. We evaluated the linkage between food insecurity and liver stiffness measurements (LSMs), a key measure of liver health. METHODS: A cross-sectional analysis of 3502 subjects aged 20 years and older from the 2017 to 2018 National Health and Nutrition Examination Survey. Food security was measured using the US Department of Agriculture's Core Food Security Module. Models were adjusted using age, sex, race/ethnicity, education, poverty-income ratio, smoking, physical activity, alcohol intake, sugary beverage intake, Healthy Eating Index-2015 score. All subjects underwent vibration-controlled transient elastography, which provides LSMs (kPa) and a measure of hepatic steatosis (controlled attenuation parameter, dB/m). LSM was stratified: <7, 7 to 9.49, 9.5 to 12.49 (advanced fibrosis), and ≥12.5 (cirrhosis) in the whole-study population and stratified by age (20 to 49 y and 50 y and older). RESULTS: There were no significant differences in mean controlled attenuation parameter, alanine aminotransferase, or aspartate aminotransferase values by food security status. However, food insecurity was associated with a higher mean LSM (6.89±0.40 kPa vs. 5.77±0.14 kPa, P =0.02) for adults 50 years and older. After multivariate adjustment, food insecurity was associated with higher LSMs across all risk stratifications for adults 50 years and older: LSM≥7 kPa [odds ratio (OR): 2.06, 95% CI, 1.06 to 4.02]; LSM≥9.5 kPa (OR: 2.50, 95% CI, 1.11 to 5.64); LSM≥12.5 kPa (OR: 3.07, 95% CI, 1.21 to 7.80). CONCLUSIONS: Food insecurity is associated with liver fibrosis and an increased risk of advanced fibrosis and cirrhosis in older adults.

Patterns of Care Utilization and Hepatocellular Carcinoma Surveillance: Tracking Care Across the Pandemic.

INTRODUCTION: We studied longitudinal trends in mortality, outpatient, and inpatient care for cirrhosis in a national cohort in the first 2 years of the coronavirus disease-2019 pandemic. We evaluated trends in hepatocellular carcinoma (HCC) surveillance and factors associated with completion. METHODS: Within the national cirrhosis cohort in the Veterans Administration from 2020 to 2021, we captured mortality, outpatient primary care provider, gastroenterology/hepatology (GI/HEP) visits, and hospitalizations. HCC surveillance was computed as percentage of time up to date with surveillance every 6 months (PTUDS). Multivariable models for PTUDS were adjusted for patient demographics, clinical factors, and facility-level variables. RESULTS: The total cohort was 68,073; 28,678 were eligible for HCC surveillance. Outpatient primary care provider and GI/HEP appointment rates initially dropped from 30% to 7% with a rebound 1 year into the pandemic and steady subsequent use. Telemedicine monthly visit rates rose from less than 10% to a peak of 20% with a steady gradual decline. Nearly 70% of Veterans were up to date with HCC surveillance before the pandemic with an early pandemic nadir of approximately 50% and 60% PTUDS 2 years into the pandemic. In adjusted models, use of a population-based cirrhosis dashboard (ß 8.5, 95% CI 6.9-10.2) and GI/HEP visits both in-person (ß 3.2, 95% CI 2.9-3.6) and telemedicine (ß 2.1, 95% CI 1.9-2.4) were associated with a higher PTUDS. DISCUSSION: Outpatient utilization and HCC surveillance rates have rebounded but remain below at baseline. Population-based approaches and specialty care for cirrhosis were associated with a higher completion of HCC surveillance.

Review article: current and emerging therapies for the management of cirrhosis and its complications.

BACKGROUND: Cirrhosis is increasingly common and morbid. Optimal utilisation of therapeutic strategies to prevent and control the complications of cirrhosis are central to improving clinical and patient-reported outcomes. METHODS: We conducted a narrative review of the literature focusing on the most recent advances. RESULTS: We review the aetiology-focused therapies that can prevent cirrhosis and its complications. These include anti-viral therapies, psychopharmacological therapy for alcohol-use disorder, and the current landscape of clinical trials for non-alcoholic steatohepatitis. We review the current standard of care and latest developments in the management of hepatic encephalopathy (HE), ascites and hepatorenal syndrome. We evaluate the promise and drawbacks of chemopreventative therapies that have been examined in trials and observational studies which may reduce the risk of hepatocellular carcinoma and cirrhosis complications. Finally, we examine the therapies which address the non-pain symptoms of cirrhosis including pruritis, muscle cramps, sexual dysfunction and fatigue. CONCLUSION: The improvement of clinical and patient-reported outcomes for patients with cirrhosis is possible by applying evidence-based pharmacotherapeutic approaches to the prevention and treatment of cirrhosis complications.

Hepatocellular Carcinoma-Related Mortality in the USA, 1999-2018.

BACKGROUND AND AIMS: The burden of hepatocellular carcinoma (HCC) is increasing, and certain groups may be at higher risk. METHODS: We analyzed trends in HCC-related mortality in the USA (1999-2018) using national death data. Age-adjusted trends in death rates (annual percentage change, APC) were calculated using joinpoint regression analysis. RESULTS: HCC-related death rates increased by 2.1% (95% CI 1.9 to 2.3) annually. Hepatitis C (HCV)-related HCC death rates increased from 1999 to 2012 (8.9%, 95% CI 7.6 to 10.2) followed by a -1.3% (95% CI -3.5 to 0.9) decrease annually. For adults > 65 years, HCV-related HCC death rates increased (7.3% annually, 95% CI 6.5 to 8.1), especially for rural areas (11.1% annually, 95% CI 6.9 to 15.5) with high rates among African-Americans and Hispanics. Increases in non-HCV-related HCC death rates were larger: 13.5% annually (95% CI 3.6 to 24.3, 2005-2010) followed by 4.2% annually (95% CI 2.3 to 6.2, 2010-2018). Annual rates of increase were similar for men (6.8%, 95% CI 5.9 to 7.8) and women (7.0%, 95% CI 5.5 to 8.4) from 1999 to 2018. Rate of increase across races was Whites 8.3% (95% CI 7.2 to 9.4, 1999-2018), African-Americans 11.2% (95% CI -6.6 to 32.3, 2015-2018), and Hispanics 3.7% (95% CI 1.0 to 6.5, 2012-2018). CONCLUSION: HCC-related mortality has increased, driven by increases in non-HCV-related mortality with important demographic and regional trends. In addition, HCV-HCC mortality remains high particularly in older persons and those in rural areas despite advances in HCV therapy. These data underscore the need for targeted approaches to mitigate the burden of HCC-related mortality similar to efforts for other cancers.

Patient-reported outcomes in HCC: A scoping review by the Practice Metrics Committee of the American Association for the Study of Liver Diseases.

BACKGROUND AND AIMS: HCC is a leading cause of mortality in patients with advanced liver disease and is associated with significant morbidity. Despite multiple available curative and palliative treatments, there is a lack of systematic evaluation of patient-reported outcomes (PROs) in HCC. APPROACH AND RESULTS: The American Association for the Study of Liver Diseases Practice Metrics Committee conducted a scoping review of PROs in HCC from 1990 to 2021 to (1) synthesize the evidence on PROs in HCC and (2) provide recommendations on incorporating PROs into clinical practice and quality improvement efforts. A total of 63 studies met inclusion criteria investigating factors associated with PROs, the relationship between PROs and survival, and associations between HCC therapy and PROs. Studies recruited heterogeneous populations, and most were cross-sectional. Poor PROs were associated with worse prognosis after adjusting for clinical factors and with more advanced disease stage, although some studies showed better PROs in patients with HCC compared to those with cirrhosis. Locoregional and systemic therapies were generally associated with a high symptom burden; however, some studies showed lower symptom burden for transarterial radiotherapy and radiation therapy. Qualitative studies identified additional symptoms not routinely assessed with structured questionnaires. Gaps in the literature include lack of integration of PROs into clinical care to guide HCC treatment decisions, unknown impact of HCC on caregivers, and the effect of palliative or supportive care quality of life and health outcomes. CONCLUSION: Evidence supports assessment of PROs in HCC; however, clinical implementation and the impact of PRO measurement on quality of care and longitudinal outcomes need future investigation.

Patient Preferences for Hepatocellular Carcinoma Surveillance Parameters.

BACKGROUND AND AIMS: Professional societies recommend abdominal ultrasound (US) with or without alpha fetoprotein (AFP) for hepatocellular cancer (HCC) surveillance; however, there are several emerging surveillance modalities, including abbreviated MRI and blood-based biomarker panels. Most studies have focused on provider perspectives for surveillance logistics, but few have assessed patient preferences. We aimed to measure preferences among patients with cirrhosis regarding HCC surveillance modalities. METHODS: We conducted a choice-based conjoint survey to patients with cirrhosis at four institutions. Participants were provided 15 scenarios in which they were asked to choose surveillance modalities based on five test attributes: benefits, i.e. sensitivity for early HCC (range: 35-95%), physical harm, i.e. false positives requiring additional testing (range: 10-40%), financial harm, i.e. out-of-pocket costs (range: $10-100), test logistics and convenience, i.e. duration of testing (range: 10-60 min). Hierarchical Bayes discrete choice conjoint analysis was used to derive attribute importance, and preference shares were determined by simulation. RESULTS: In total 91% (182/199) of approached patients consented to participate in the study and 98% (n=179) successfully completed the survey. Surveillance benefits (importance: 51.3%, 95%CI: 49.0-53.4%) were valued more than risk of physical harm (importance: 7.6%, 95%CI 7.0-8.2%), financial harm (importance: 15.2%, 95%CI 14.0-16.3%), convenience (importance: 9.3%, 95%CI 8.5-10.1%) and test logistics (importance: 16.7%, 95%CI 15.4-18.1%). Based on simulations including all possible tests, patients preferred abbreviated MRI (29.0%), MRI (23.3%), or novel blood-based biomarkers (20.9%) to ultrasound alone (3.4%) or with AFP (8.8%). CONCLUSIONS: Patients with cirrhosis prioritize early HCC detection over potential surveillance-related harms or inconvenience.

Gamma-Glutamyl Transferase (γ-GT) - an old dog with new tricks?

Gamma-Glutamyl Transferase (γGT) is a key transferase involved in the transpeptidation of functional gamma-glutamyl groups to various receptor moieties. It performs important roles in antioxidant defence mechanisms, particularly glutathione recycling, xenobiotic metabolism, but analogously may also have a pro-oxidant role. γGT is very sensitive for the diagnosis of liver injury, although it has poor specificity for particular aetiologies. It has been used to reflect temporal changes as a form of monitoring depending on aetiology. Given its cellular role in antioxidant function, it has been investigated as a surrogate biomarker of oxidative stress. It has also been found to be a predictor of mortality across a spectra of non-hepatic disease pathologies, from metabolic and cardiovascular risk to chronic kidney disease and neoplasia. Similarly, it also remains of interest to the insurance industry given an apparent ability to predict mortality, in addition to a historical interest from law enforcement as a marker of chronic alcohol ingestion. Here, we review some of the unique characteristics of this important enzyme, previously considered as a mere specific marker of liver dysfunction, but now with clear extra-hepatic implications and novel applications and utility.

Quality measures in HCC care by the Practice Metrics Committee of the American Association for the Study of Liver Diseases.

The burden of HCC is substantial. To address gaps in HCC care, the American Association for the Study of Liver Diseases (AASLD) Practice Metrics Committee (PMC) aimed to develop a standard set of process-based measures and patient-reported outcomes (PROs) along the HCC care continuum. We identified candidate process and outcomes measures for HCC care based on structured literature review. A 13-member panel with content expertise across the HCC care continuum evaluated candidate measures on importance and performance gap using a modified Delphi approach (two rounds of rating) to define the final set of measures. Candidate PROs based on a structured scoping review were ranked by 74 patients with HCC across 7 diverse institutions. Out of 135 measures, 29 measures made the final set. These covered surveillance (6 measures), diagnosis (6 measures), staging (2 measures), treatment (10 measures), and outcomes (5 measures). Examples included the use of ultrasound (± alpha-fetoprotein [AFP]) every 6 months, need for surveillance in high-risk populations, diagnostic testing for patients with a new AFP elevation, multidisciplinary liver tumor board (MLTB) review of Liver Imaging-Reporting and Data System 4 lesions, standard evaluation at diagnosis, treatment recommendations based on Barcelona Clinic Liver Cancer staging, MLTB discussion of treatment options, appropriate referral for evaluation of liver transplantation candidacy, and role of palliative therapy. PROs include those related to pain, anxiety, fear of treatment, and uncertainty about the best individual treatment and the future. The AASLD PMC has developed a set of explicit quality measures in HCC care to help bridge the gap between guideline recommendations and measurable processes and outcomes. Measurement and subsequent implementation of these metrics could be a central step in the improvement of patient care and outcomes in this high-risk population.

Effect of increased alcohol consumption during COVID-19 pandemic on alcohol-associated liver disease: A modeling study.

BACKGROUND AND AIMS: Alcohol consumption increased during the COVID-19 pandemic in 2020 in the United States. We projected the effect of increased alcohol consumption on alcohol-associated liver disease (ALD) and mortality. APPROACH AND RESULTS: We extended a previously validated microsimulation model that estimated the short- and long-term effect of increased drinking during the COVID-19 pandemic in individuals in the United States born between 1920 and 2012. We modeled short- and long-term outcomes of current drinking patterns during COVID-19 (status quo) using survey data of changes in alcohol consumption in a nationally representative sample between February and November 2020. We compared these outcomes with a counterfactual scenario wherein no COVID-19 occurs and drinking patterns do not change. One-year increase in alcohol consumption during the COVID-19 pandemic is estimated to result in 8000 (95% uncertainty interval [UI], 7500-8600) additional ALD-related deaths, 18,700 (95% UI, 17,600-19,900) cases of decompensated cirrhosis, and 1000 (95% UI, 1000-1100) cases of HCC, and 8.9 million disability-adjusted life years between 2020 and 2040. Between 2020 and 2023, alcohol consumption changes due to COVID-19 will lead to 100 (100-200) additional deaths and 2800 (2700-2900) additional decompensated cirrhosis cases. A sustained increase in alcohol consumption for more than 1 year could result in additional morbidity and mortality. CONCLUSIONS: A short-term increase in alcohol consumption during the COVID-19 pandemic can substantially increase long-term ALD-related morbidity and mortality. Our findings highlight the need for individuals and policymakers to make informed decisions to mitigate the impact of high-risk alcohol drinking in the United States.

Cognitive Function, Sarcopenia, and Inflammation Are Strongly Associated with Frailty: A Framingham Cohort Study.

BACKGROUND: Frailty is an important contributor to morbidity and mortality in chronic liver disease. Understanding the contributors to frailty has the potential to identify individuals at risk for frailty and may potentially provide targets for frailty-modifying interventions. We evaluated the relationship among cognitive function, inflammation, and sarcopenia and frailty. METHODS: Using cohorts from the Framingham Heart Study (2011-2014), we evaluated for factors associated with frailty. Exposures included cognitive tests (combined Trails A/B test, Animal Naming Test, and combined Digit Span Forward/Backward test), inflammation (interleukin-6 and tumor necrosis factor receptor II), and sarcopenia (creatinine-to-cystatin C ratio). We performed linear and logistic regression to identify the relationship between these exposures and the Liver Frailty Index (LFI). RESULTS: The study population (N = 1208) had a median age of 70 years, was 56% female, and 48.5% had evidence of liver disease. The combined Trails A/B test (ß 0.05, P < .001), creatinine-to-cystatin C (ß -0.17, P = .006), and both inflammatory markers, interleukin-6 levels (ß 0.16, P = .002) and tumor necrosis factor receptor II (ß 0.21, P = .04), were independently associated with the LFI. Using an LFI cutoff of ≥4.5 to define frailty, Trails A/B (odds ratio [OR] 1.21, 95% confidence interval [CI] 1.07-1.37), Animal Naming Test (OR 0.64, 95% CI 0.42-0.97), sarcopenia (OR 0.10, 95% CI 0.01-0.73), and interleukin-6 (OR 4.99, 95% CI 1.03-15.53) were all associated with frailty. Although liver disease did not modify the relationship between the LFI and the Trails A/B test, interleukin-6 was significantly associated with the LFI only in the presence of liver disease. CONCLUSIONS: Cognitive performance, inflammation, and sarcopenia, each highly prevalent in cirrhosis, are associated with the LFI in this population-based study of persons without cirrhosis. Further research is warranted for interventions aiming to prevent frailty by tailoring their approach to the patient's underlying risk factors.