MASLD/MetALD and mortality in individuals with any cardio-metabolic risk factor: A population-based study with 26.7 years of follow-up.

BACKGROUND AND AIMS: A new term, metabolic dysfunction-associated steatotic liver disease (MASLD), has been proposed by a multi-society expert panel. However, it remains unclear whether hepatic steatosis per se in MASLD contributes to an increased risk of mortality in individuals with any cardio-metabolic risk factor (CMRF), which is also a significant risk factor for increased mortality. This study aimed to compare all-cause and cause-specific mortality between the "MASLD/MetALD" and "no steatotic liver disease (SLD)" groups in individuals with any CMRF. APPROACH AND RESULTS: A population-based cohort study was conducted using 10,750 participants of the Third National Health and Nutrition Examination Survey. All-cause and cause-specific (cardiovascular, cancer, diabetes, and liver) mortality risks were compared between the "MASLD," "MetALD," and "no SLD" groups using the Cox proportional hazards model with complex survey design weights, adjusted for confounders. Over 26 years, the "MASLD" group did not show significantly increased all-cause (adjusted HR 1.04[95% CI: 0.95-1.14], p = 0.413), cardiovascular (0.88 [0.75-1.04], p = 0.139), or cancer (1.06[0.84-1.33], p = 0.635) mortality risk compared to the "no SLD" group in individuals with any CMRF. The MetALD group was associated with increased all-cause (1.41 [1.05-1.89], p = 0.022), cancer (2.35 [1.33-4.16], p = 0.004), and liver (15.04 [2.96-76.35], p = 0.002) mortality risk compared with the no SLD group. This trend was more pronounced in the MetALD group with advanced fibrosis assessed by Fibrosis-4 (FIB-4). CONCLUSIONS: In individuals with CMRF, the presence of steatotic liver disease (MASLD) alone did not increase the risk of mortality, except in cases with more alcohol consumption (MetALD). Therefore controlling metabolic risk factors and reducing alcohol consumption in people with MASLD or MetALD will be crucial steps to improve long-term health outcomes.

Impact of pre-transplant immune checkpoint inhibitor use on post-transplant outcomes in HCC: A systematic review and individual patient data meta-analysis.

BACKGROUND & AIMS: Treatment with immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC) prior to liver transplantation (LT) has been reported; however, ICIs may elevate the risk of allograft rejection and impact other clinical outcomes. This study aims to summarize the impact of ICI use on post-LT outcomes. METHODS: In this individual patient data meta-analysis, we searched databases to identify HCC cases treated with ICIs before LT, detailing allograft rejection, HCC recurrence, and overall survival. We performed Cox regression analysis to identify risk factors for allograft rejection. RESULTS: Among 91 eligible patients, with a median (IQR) follow-up of 690.0 (654.5) days, there were 24 (26.4%) allograft rejections, 9 (9.9%) HCC recurrences, and 9 (9.9%) deaths. Age (adjusted hazard ratio [aHR] per 10 years 0.72, 95% CI 0.53-0.99, p = 0.044) and ICI washout time (aHR per 1 week 0.92, 95% CI 0.86-0.99, p = 0.022) were associated with allograft rejection. The median (IQR) washout period for patients with ≤20% probability of allograft rejection was 94 (196) days. Overall survival did not differ between cases with and without allograft rejection (log-rank test, p = 0.2). Individuals with HCC recurrence had fewer median (IQR) ICI cycles than those without recurrence (4.0 [1.8] vs. 8.0 [9.0]; p = 0.025). The proportion of patients within Milan post-ICI was lower for those with recurrence vs. without (16.7% vs. 65.3%, p = 0.032). CONCLUSION: Patients have acceptable post-LT outcomes after ICI therapy. Age and ICI washout length relate to the allograft rejection risk, and a 3-month washout may reduce it to that of patients without ICI exposure. Number of ICI cycles and tumor burden may affect recurrence risk. Large prospective studies are necessary to confirm these associations. IMPACT AND IMPLICATIONS: This systematic review and individual patient data meta-analysis of 91 patients with hepatocellular carcinoma and immune checkpoint inhibitor use prior to liver transplantation suggest acceptable overall post-transplant outcomes. Older age and longer immune checkpoint inhibitor washout period have a significant inverse association with the risk of allograft rejection. A 3-month washout may reduce it to that of patients without immune checkpoint inhibitor exposure. Additionally, a higher number of immune checkpoint inhibitor cycles and tumor burden within Milan criteria at the completion of immunotherapy may predict a decreased risk of hepatocellular carcinoma recurrence, but this observation requires further validation in larger prospective studies.

Machine Learning-Based Models for Advanced Fibrosis and Cirrhosis Diagnosis in Chronic Hepatitis B Patients With Hepatic Steatosis.

BACKGROUND AND AIMS: The global rise of chronic hepatitis B (CHB) superimposed on hepatic steatosis (HS) warrants noninvasive, precise tools for assessing fibrosis progression. This study leveraged machine learning (ML) to develop diagnostic models for advanced fibrosis and cirrhosis in this patient population. METHODS: Treatment-naive CHB patients with concurrent HS who underwent liver biopsy in 10 medical centers were enrolled as a training cohort and an independent external validation cohort (NCT05766449). Six ML models were implemented to predict advanced fibrosis and cirrhosis. The final models, derived from SHAP (Shapley Additive exPlanations), were compared with Fibrosis-4 Index, nonalcoholic fatty liver disease Fibrosis Score, and aspartate aminotransferase-to-platelet ratio index using the area under receiver-operating characteristic curve (AUROC) and decision curve analysis (DCA). RESULTS: Of 1,198 eligible patients, the random forest model achieved AUROCs of 0.778 (95% confidence interval [CI], 0.749-0.807) for diagnosing advanced fibrosis (random forest advanced fibrosis model) and 0.777 (95% CI, 0.748-0.806) for diagnosing cirrhosis (random forest cirrhosis model) in the training cohort, and maintained high AUROCs in the validation cohort. In the training cohort, the random forest advanced fibrosis model obtained an AUROC of 0.825 (95% CI, 0.787-0.862) in patients with hepatitis B virus DNA ≥105 IU/mL, and the random forest cirrhosis model had an AUROC of 0.828 (95% CI, 0.774-0.883) in female patients. The 2 models outperformed Fibrosis-4 Index, nonalcoholic fatty liver disease Fibrosis Score, and aspartate aminotransferase-to-platelet ratio index in the training cohort, and also performed well in the validation cohort. CONCLUSIONS: The random forest models provide reliable, noninvasive tools for identifying advanced fibrosis and cirrhosis in CHB patients with concurrent HS, offering a significant advancement in the comanagement of the 2 diseases. CLINICALTRIALS: gov, Number: NCT05766449.

Machine learning versus multivariate logistic regression for predicting severe COVID-19 in hospitalized children with Omicron variant infection.

With the emergence of the Omicron variant, the number of pediatric Coronavirus Disease 2019 (COVID-19) cases requiring hospitalization and developing severe or critical illness has significantly increased. Machine learning and multivariate logistic regression analysis were used to predict risk factors and develop prognostic models for severe COVID-19 in hospitalized children with the Omicron variant in this study. Of the 544 hospitalized children including 243 and 301 in the mild and severe groups, respectively. Fever (92.3%) was the most common symptom, followed by cough (79.4%), convulsions (36.8%), and vomiting (23.2%). The multivariate logistic regression analysis showed that age (1-3 years old, odds ratio (OR): 3.193, 95% confidence interval (CI): 1.778-5.733], comorbidity (OR: 1.993, 95% CI:1.154-3.443), cough (OR: 0.409, 95% CI:0.236-0.709), and baseline neutrophil-to-lymphocyte ratio (OR: 1.108, 95% CI: 1.023-1.200), lactate dehydrogenase (OR: 1.993, 95% CI: 1.154-3.443), blood urea nitrogen (OR: 1.002, 95% CI: 1.000-1.003) and total bilirubin (OR: 1.178, 95% CI: 1.005-3.381) were independent risk factors for severe COVID-19. The area under the curve (AUC) of the prediction models constructed by multivariate logistic regression analysis and machine learning (RandomForest + TomekLinks) were 0.7770 and 0.8590, respectively. The top 10 most important variables of random forest variables were selected to build a prediction model, with an AUC of 0.8210. Compared with multivariate logistic regression, machine learning models could more accurately predict severe COVID-19 in children with Omicron variant infection.

Different minimal alcohol consumption in male and female individuals with metabolic dysfunction-associated fatty liver disease.

BACKGROUND AND AIMS: The relationship between moderate alcohol intake and health outcomes among individuals with metabolic dysfunction-associated fatty liver disease (MAFLD) is complex. Our aim was to investigate the association of minimal alcohol consumption with all-cause and cause-specific mortality among MAFLD individuals of different genders. METHODS: Our study included 2630 MAFLD individuals from the Third National Health and Nutrition Examination Survey. Cox regression analysis was performed to assess the association between alcohol use measures and all-cause and cause-specific mortality. Restricted cubic spline curves were used to evaluate the relationship between alcohol consumption per week and all-cause mortality. RESULTS: In the entire MAFLD cohort, we observed significant disparities in clinical characteristics between male and female individuals with MAFLD. Higher weekly alcohol consumption was significantly associated with all-cause and cause-specific mortality (male, hazard ratios [HRs]: 1.009, 95% CIs: 1.004-1.014; female, HRs: 1.032, 95% CIs: 1.022-1.042). In males with MAFLD, a linear association with all-cause mortality was observed for weekly alcohol consumption (p for non-linearity = .21). Conversely, in females with MAFLD, the risk of all-cause mortality remained relatively stable until 2 drinks per week, after which it rapidly increased with each additional drink consumed, and the increase in mortality risk was higher than that observed in males (p for non-linearity < .05). CONCLUSIONS: Our findings indicate that any increase in weekly alcohol consumption was associated with increased all-cause mortality in men with MAFLD. Conversely, consuming less than 2 drinks per week had minimal impact on the risk of mortality among female.

Large language models and bariatric surgery patient education: a comparative readability analysis of GPT-3.5, GPT-4, Bard, and online institutional resources.

BACKGROUND: The readability of online bariatric surgery patient education materials (PEMs) often surpasses the recommended 6th grade level. Large language models (LLMs), like ChatGPT and Bard, have the potential to revolutionize PEM delivery. We aimed to evaluate the readability of PEMs produced by U.S. medical institutions compared to LLMs, as well as the ability of LLMs to simplify their responses. METHODS: Responses to frequently asked questions (FAQs) related to bariatric surgery were gathered from top-ranked health institutions. FAQ responses were also generated from GPT-3.5, GPT-4, and Bard. LLMs were then prompted to improve the readability of their initial responses. The readability of institutional responses, initial LLM responses, and simplified LLM responses were graded using validated readability formulas. Accuracy and comprehensiveness of initial and simplified LLM responses were also compared. RESULTS: Responses to 66 FAQs were included. All institutional and initial LLM responses had poor readability, with average reading levels ranging from 9th grade to college graduate. Simplified responses from LLMs had significantly improved readability, with reading levels ranging from 6th grade to college freshman. When comparing simplified LLM responses, GPT-4 responses demonstrated the highest readability, with reading levels ranging from 6th to 9th grade. Accuracy was similar between initial and simplified responses from all LLMs. Comprehensiveness was similar between initial and simplified responses from GPT-3.5 and GPT-4. However, 34.8% of Bard's simplified responses were graded as less comprehensive compared to initial. CONCLUSION: Our study highlights the efficacy of LLMs in enhancing the readability of bariatric surgery PEMs. GPT-4 outperformed other models, generating simplified PEMs from 6th to 9th grade reading levels. Unlike GPT-3.5 and GPT-4, Bard's simplified responses were graded as less comprehensive. We advocate for future studies examining the potential role of LLMs as dynamic and personalized sources of PEMs for diverse patient populations of all literacy levels.

Appropriateness of ChatGPT in Answering Heart Failure Related Questions.

BACKGROUND: Heart failure requires complex management, and increased patient knowledge has been shown to improve outcomes. This study assessed the knowledge of Chat Generative Pre-trained Transformer (ChatGPT) and its appropriateness as a supplemental resource of information for patients with heart failure. METHOD: A total of 107 frequently asked heart failure-related questions were included in 3 categories: "basic knowledge" (49), "management" (41) and "other" (17). Two responses per question were generated using both GPT-3.5 and GPT-4 (i.e., two responses per question per model). The accuracy and reproducibility of responses were graded by two reviewers, board-certified in cardiology, with differences resolved by a third reviewer, board-certified in cardiology and advanced heart failure. Accuracy was graded using a four-point scale: (1) comprehensive, (2) correct but inadequate, (3) some correct and some incorrect, and (4) completely incorrect. RESULTS: GPT-4 provided 107/107 (100%) responses with correct information. Further, GPT-4 displayed a greater proportion of comprehensive knowledge for the categories of "basic knowledge" and "management" (89.8% and 82.9%, respectively). For GPT-3, there were two total responses (1.9%) graded as "some correct and incorrect" for GPT-3.5, while no "completely incorrect" responses were produced. With respect to comprehensive knowledge, GPT-3.5 performed best in the "management" category and "other" category (prognosis, procedures, and support) (78.1%, 94.1%). The models also provided highly reproducible responses, with GPT-3.5 scoring above 94% in every category and GPT-4 with 100% for all answers. CONCLUSIONS: GPT-3.5 and GPT-4 answered the majority of heart failure-related questions accurately and reliably. If validated in future studies, ChatGPT may serve as a useful tool in the future by providing accessible health-related information and education to patients living with heart failure. In its current state, ChatGPT necessitates further rigorous testing and validation to ensure patient safety and equity across all patient demographics.

Impact of the COVID-19 pandemic on liver disease-related mortality rates in the United States.

BACKGROUND & AIMS: The pandemic has resulted in an increase of deaths not directly related to COVID-19 infection. We aimed to use a national death dataset to determine the impact of the pandemic on people with liver disease in the USA, focusing on alcohol-associated liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). METHODS: Using data from the National Vital Statistic System from the Center for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) platform and ICD-10 codes, we identified deaths associated with liver disease. We evaluated observed vs. predicted mortality for 2020-2021 based on trends from 2010-2019 with joinpoint and prediction modelling analysis. RESULTS: Among 626,090 chronic liver disease-related deaths between 2010 and 2021, Age-standardised mortality rates (ASMRs) for ALD dramatically increased between 2010-2019 and 2020-2021 (annual percentage change [APC] 3.5% to 17.6%, p <0.01), leading to a higher observed ASMR (per 100,000 persons) than predicted for 2020 (15.67 vs. 13.04) and 2021 (17.42 vs. 13.41). ASMR for NAFLD also increased during the pandemic (APC: 14.5%), whereas the rates for hepatitis B and C decreased. Notably, the ASMR rise for ALD was most pronounced in non-Hispanic Whites, Blacks, and Alaska Indians/Native Americans (APC: 11.7%, 10.8%, 18.0%, all p <0.05), with similar but less critical findings for NAFLD, whereas rates were steady for non-Hispanic Asians throughout 2010-2021 (APC: 4.9%). The ASMR rise for ALD was particularly severe for the 25-44 age group (APC: 34.6%, vs. 13.7% and 12.6% for 45-64 and ≥65, all p <0.01), which were also all higher than pre-COVID-19 rates (all p <0.01). CONCLUSIONS: ASMRs for ALD and NAFLD increased at an alarming rate during the COVID-19 pandemic with the largest disparities among the young, non-Hispanic White, and Alaska Indian/Native American populations. IMPACT AND IMPLICATIONS: The pandemic has led to an increase of deaths directly and indirectly related to SARS-CoV-2 infection. As shown in this study, age-standardised mortality rates for alcohol-associated liver disease and non-alcoholic fatty liver disease substantially increased during the COVID-19 pandemic in the USA and far exceeded expected levels predicted from past trends, especially among the young, non-Hispanic White, and Alaska Indian/Native American populations. However, much of this increase was not directly related to COVID-19. Therefore, for the ongoing pandemic as well as its recovery phase, adherence to regular monitoring and care for people with chronic liver disease should be prioritised and awareness should be raised among patients, care providers, healthcare systems, and public health policy makers.

Racial and Ethnic Disparities in Years of Potential Life Loss Among Patients With Cirrhosis During the COVID-19 Pandemic in the United States.

INTRODUCTION: Our aim was to evaluate the impact of race/ethnicity on cirrhosis-related premature death during the COVID-19 pandemic. METHODS: We obtained cirrhosis-related death data (n = 872,965, January 1, 2012-December 31, 2021) from the US National Vital Statistic System to calculate age-standardized mortality rates and years of potential life lost (YPLL) for premature death aged 25-64 years. RESULTS: Significant racial/ethnic disparity in cirrhosis-related age-standardized mortality rates was noted prepandemic but widened during the pandemic, with the highest excess YPLL for the non-Hispanic American Indian/American Native (2020: 41.0%; 2021: 68.8%) followed by other minority groups (28.7%-45.1%), and the non-Hispanic White the lowest (2020: 20.7%; 2021: 31.6%). COVID-19 constituted >30% of the excess YPLLs for Hispanic and non-Hispanic American Indian/American Native in 2020, compared with 11.1% for non-Hispanic White. DISCUSSION: Ethnic minorities with cirrhosis experienced a disproportionate excess death and YPLLs in 2020-2021.

Immunotherapy and Transarterial Radioembolization Combination Treatment for Advanced Hepatocellular Carcinoma.

INTRODUCTION: The efficacy and safety of combined immunotherapy and transarterial radioembolization (TARE) were suggested in preclinical and early-phase trials, but these were limited by small sample sizes. We sought to compare the efficacy of combined therapy and immunotherapy alone in patients with advanced hepatocellular carcinoma (HCC). METHODS: The National Cancer Database was used to identify patients with advanced HCC diagnosed between January 1, 2017, and December 31, 2019. We included patients who received combined therapy or immunotherapy alone as first-line treatment. Multivariable logistic regression was conducted to determine predictors of combined therapy. Kaplan-Meier and Cox regression approaches were used to identify predictors of overall survival and to compare hazards of mortality between the patients who received combined therapy and immunotherapy alone. RESULTS: Of 1,664 eligible patients with advanced-stage HCC, 142 received combined TARE/immunotherapy and 1,522 received immunotherapy alone. Receipt of combination therapy was associated with care at an academic center and inversely associated with racial/ethnic minority status (Hispanic and Black individuals). The median overall survival was significantly higher in the combination group than in the immunotherapy alone group (19.8 vs 9.5 months). In multivariable analysis, combined therapy was independently associated with reduced mortality (adjusted hazard ratio 0.50, 95% confidence interval: 0.36-0.68, P < 0.001). Results were consistent across subgroups and in sensitivity analyses using propensity score matching and inverse probability of treatment weighting. DISCUSSION: The combination of TARE and immunotherapy was associated with improved survival compared with immunotherapy alone in patients with advanced-stage HCC. Our findings underly the importance of large clinical trials evaluating combination therapy in these patients.

HIV-related mortality in the United States during the COVID-19 pandemic: A population-based study.

BACKGROUND: US progress toward ending the HIV epidemic was disrupted during the COVID-19 pandemic. OBJECTIVES: To determine the impact of the pandemic on HIV-related mortality and potential disparities. METHODS: Using data from the Centers for Disease Control and Prevention and the United States (US) Census Bureau, HIV-related mortality data of decedents aged ≥25 years between 2012 and 2021 were analyzed. Excess HIV-related mortality rates were estimated by determining the difference between observed and projected mortality rates during the pandemic. The trends of mortality were quantified with joinpoint regression analysis. RESULTS: Of the 79,725 deaths documented in adults aged 25 years and older between 2012 and 2021, a significant downward trend was noted in HIV-related mortality rates before the pandemic, followed by a surge during the pandemic. The observed mortality rates were 18.8% (95% confidence interval [CI]: 13.1%-25.5%) and 25.4% (95%CI: 19.9%-30.4%) higher than the projected values in 2020 and 2021, respectively. Both of these percentages were higher than that in the general population in 2020 (16.4%, 95%CI: 14.9%-17.9%) and 2021 (19.8%, 95%CI: 18.0%-21.6%), respectively. Increased HIV-related mortality was observed across all age subgroups, but those aged 25-44 years demonstrated the greatest relative increase and the lowest COVID-19-related deaths when compared to middle- and old-aged decedents. Disparities were observed across racial/ethnic subgroups and geographic regions. CONCLUSIONS: The pandemic led to a reversal in the attainments made to reduce the prevalence of HIV. Individuals living with HIV were disproportionately affected during the pandemic. Thoughtful policies are needed to address the disparity in excess HIV-related mortality.

Optimizing hepatitis B virus screening in the United States using a simple demographics-based model.

BACKGROUND AND AIMS: Chronic hepatitis B (CHB) affects >290 million persons globally, and only 10% have been diagnosed, presenting a severe gap that must be addressed. We developed logistic regression (LR) and machine learning (ML; random forest) models to accurately identify patients with HBV, using only easily obtained demographic data from a population-based data set. APPROACH AND RESULTS: We identified participants with data on HBsAg, birth year, sex, race/ethnicity, and birthplace from 10 cycles of the National Health and Nutrition Examination Survey (1999-2018) and divided them into two cohorts: training (cycles 2, 3, 5, 6, 8, and 10; n = 39,119) and validation (cycles 1, 4, 7, and 9; n = 21,569). We then developed and tested our two models. The overall cohort was 49.2% male, 39.7% White, 23.2% Black, 29.6% Hispanic, and 7.5% Asian/other, with a median birth year of 1973. In multivariable logistic regression, the following factors were associated with HBV infection: birth year 1991 or after (adjusted OR [aOR], 0.28; p < 0.001); male sex (aOR, 1.49; p = 0.0080); Black and Asian/other versus White (aOR, 5.23 and 9.13; p < 0.001 for both); and being USA-born (vs. foreign-born; aOR, 0.14; p < 0.001). We found that the ML model consistently outperformed the LR model, with higher area under the receiver operating characteristic values (0.83 vs. 0.75 in validation cohort; p < 0.001) and better differentiation of high- and low-risk persons. CONCLUSIONS: Our ML model provides a simple, targeted approach to HBV screening, using only easily obtained demographic data.

Excess risk for acute myocardial infarction mortality during the COVID-19 pandemic.

The COVID-19 pandemic has had a detrimental impact on the healthcare system. Our study armed to assess the extent and the disparity in excess acute myocardial infarction (AMI)-associated mortality during the pandemic, through the recent Omicron outbreak. Using data from the CDC's National Vital Statistics System, we identified 1 522 669 AMI-associated deaths occurring between 4/1/2012 and 3/31/2022. Accounting for seasonality, we compared age-standardized mortality rate (ASMR) for AMI-associated deaths between prepandemic and pandemic periods, including observed versus predicted ASMR, and examined temporal trends by demographic groups and region. Before the pandemic, AMI-associated mortality rates decreased across all subgroups. These trends reversed during the pandemic, with significant rises seen for the youngest-aged females and males even through the most recent period of the Omicron surge (10/2021-3/2022). The SAPC in the youngest and middle-age group in AMI-associated mortality increased by 5.3% (95% confidence interval [CI]: 1.6%-9.1%) and 3.4% (95% CI: 0.1%-6.8%), respectively. The excess death, defined as the difference between the observed and the predicted mortality rates, was most pronounced for the youngest (25-44 years) aged decedents, ranging from 23% to 34% for the youngest compared to 13%-18% for the oldest age groups. The trend of mortality suggests that age and sex disparities have persisted even through the recent Omicron surge, with excess AMI-associated mortality being most pronounced in younger-aged adults.

Liver Complications in Untreated Treatment-Ineligible versus Treated Treatment-Eligible Patients with Hepatitis B.

BACKGROUND: A substantial number of patients who do not meet treatment criteria for chronic hepatitis B (CHB) later develop adverse outcomes such as cirrhosis and hepatocellular carcinoma (HCC). Our aim was to determine whether current practice guidelines adequately identify CHB patients who will benefit from antiviral therapy. METHODS: We performed a retrospective cohort study comparing the incidence of adverse liver outcomes (cirrhosis and/or HCC) in untreated treatment-ineligible (at baseline and throughout follow-up) versus treated treatment-eligible patients according to standard American Association for the Study of Liver Diseases (AASLD) 2018 guidance (alanine aminotransferase [ALT] >70/50 U/L for men/women plus hepatitis B virus [HBV] DNA >20,000/2,000 IU/mL for HBeAg+/-) and with a sensitivity analyses using a lower threshold (ALT >40 U/L and HBV DNA >2,000 IU/mL). RESULTS: We reviewed records of 5,840 patients from 5 clinics in California and identified 2,987 treatment-naive non-HCC CHB patients. Of those, 271 patients remained untreated treatment-ineligible, 514 patients were treatment-eligible and initiated treatment, with 5-year cumulative adverse liver incidences of 12.5% versus 7.2%, p = 0.074. On multivariable analysis adjusting for age, sex, diabetes, albumin, platelet count, and HBV DNA, compared to treated treatment-eligible patients, untreated treatment-ineligible patients had a significantly higher risk of adverse liver outcomes (adjusted hazard ratio: 2.38, 95% confidence interval 1.03-5.48, p = 0.04) in main analysis by AASLD 2018 criteria but not in sensitivity analysis using the lower treatment threshold (p = 0.09). CONCLUSION: Patients never meeting standard AASLD 2018 criteria for antiviral therapy and never treated had twice the risk of developing cirrhosis and/or HCC when compared to eligible and treated patients.

Excess psoriasis and psoriatic arthritis mortality during the COVID-19 pandemic in the United States: A nationwide population-based study from 2010 to 2021.

BACKGROUND: Little is known about mortality trends among patients with psoriasis (PsO) and psoriatic arthritis (PsA) in the United States. OBJECTIVES: To ascertain mortality trends of PsO and PsA between 2010 and 2021, focusing on the effects of the COVID-19 pandemic. METHODS: We collected data from the National Vital Statistic System and calculated age-standardized mortality rates (ASMR) and cause-specific mortality for PsO/PsA. We evaluated observed versus predicted mortality for 2020-2021 based on trends from 2010 to 2019 with joinpoint and prediction modelling analysis. RESULTS: Among 5810 and 2150 PsO- and PsA-related deaths between 2010 and 2021, ASMR for PsO dramatically increased between 2010-2019 and 2020-2021 (annual percentage change [APC] 2.07% vs. 15.26%; p < 0.01), leading to a higher observed ASMR (per 100,000 persons) than predicted for 2020 (0.27 vs. 0.22) and 2021 (0.31 vs. 0.23). The excess mortality of PsO was 22.7% and 34.8% higher than that in the general population in 2020 (16.4%, 95% CI: 14.9%-17.9%) and 2021 (19.8%, 95% CI: 18.0%-21.6%) respectively. Notably, the ASMR rise for PsO was most pronounced in the female (APC: 26.86% vs. 12.19% in males) and the middle-aged group (APC: 17.67% vs. 12.47% in the old-age group). ASMR, APC and excess mortality for PsA were similar to PsO. SARS-CoV-2 infection contributed to more than 60% of the excess mortality for PsO and PsA. CONCLUSIONS: Individuals living with PsO and PsA were disproportionately affected during the COVID-19 pandemic. Both ASMRs increased at an alarming rate, with the most pronounced disparities among the female and middle-aged groups.

Substantial gaps in evaluation and treatment of patients with hepatitis B in the US.

BACKGROUND & AIMS: The occurrence of HBV-associated liver complications is reduced by antiviral therapy. However, prior studies using local institutional cohorts have suggested that evaluation and treatment are suboptimal. We aimed to determine the proportion of patients with chronic HBV infection who received adequate evaluation, were treatment eligible, and received antiviral treatment using a large, nationwide cohort. METHODS: This retrospective analysis utilized claims data of approximately 73 million enrollees across the US from Optum's de-identified Clinformatics® Data Mart Database, 2003-2019. Adults observed for ≥6 months before and after an index diagnosis of chronic HBV infection were identified via ICD-9/ICD-10 codes, with the diagnosis confirmed by positive HBsAg, HBeAg or HBV DNA PCR. RESULTS: We included 12,608 eligible patients in the study analysis (mean age 45.7 years, 52.1% male, 54.6% Asian, 18.1% Caucasian, 10.5% African American). About half of the cohort (n = 6,559, 52.3%) did not have a complete laboratory evaluation (defined as having HBeAg, HBV DNA, and ALT tests) and only 72.4% (n = 9,129) had an "adequate" evaluation (at least HBV DNA and ALT) during the entire study period. Of those with an adequate evaluation, 11.2% were treatment eligible by AASLD criteria and 13.9% by EASL criteria; 60.4% of AASLD eligible patients and 54.3% of EASL eligible patients received treatment within 12 months from becoming eligible. CONCLUSIONS: Half of patients with chronic HBV infection in the US with private insurance did not have a complete laboratory assessment. Over one-third of treatment-eligible patients did not receive antiviral therapy. Patients who visited a specialist had a higher chance of receiving adequate evaluation and treatment. Urgent intervention is needed to identify and address the barriers to optimal care. LAY SUMMARY: In this study, we used a national database that includes laboratory data in addition to medical and pharmacy claims data to assess the current real-world management of chronic HBV infection in the US. Among the 12,608 patients with chronic HBV infection included in our study, 52.3% never had a complete laboratory evaluation and only 73% had an adequate evaluation. Among those who were treatment eligible according to major society guidelines, only 60.4% and 54.3% received treatment within 12 months, respectively.

Effect of sarcopenia on survival in patients with cirrhosis: A meta-analysis.

BACKGROUND & AIMS: The association between sarcopenia and prognosis in patients with cirrhosis remains to be determined. In this study, we aimed to quantify the association between sarcopenia and the risk of mortality in patients with cirrhosis, stratified by sex, underlying liver disease etiology, and severity of hepatic dysfunction. METHODS: PubMed, Web of Science, EMBASE, and major scientific conference sessions were searched without language restriction through 13 January 2021 with an additional manual search of bibliographies of relevant articles. Cohort studies of ≥100 patients with cirrhosis and ≥12 months of follow-up that evaluated the association between sarcopenia, muscle mass and the risk of mortality were included. RESULTS: Twenty-two studies involving 6,965 patients with cirrhosis were included. The pooled prevalence of sarcopenia in patients with cirrhosis was 37.5% overall (95% CI 32.4%-42.8%), and was higher in male patients, those with alcohol-associated liver disease, those with Child-Pugh grade C cirrhosis, and when sarcopenia was defined by L3-SMI (third lumbar-skeletal muscle index). Sarcopenia was associated with an increased risk of mortality in patients with cirrhosis (adjusted hazard ratio [aHR] 2.30, 95% CI 2.01-2.63), with similar findings in a sensitivity analysis of patients with cirrhosis without hepatocellular carcinoma (aHR 2.35, 95% CI 1.95-2.83) and in subgroups stratified by sex, liver disease etiology, and severity of hepatic dysfunction. The association between quantitative muscle mass index and mortality further supports the association between sarcopenia and poor prognosis (aHR 0.95, 95% CI 0.93-0.98). There was no significant heterogeneity in any of our analyses. CONCLUSIONS: Sarcopenia was highly and independently associated with higher risk of mortality in patients with cirrhosis. LAY SUMMARY: The prevalence of sarcopenia and its association with death in patients with cirrhosis remain unclear. This meta-analysis indicated that sarcopenia affected about one-third of patients with cirrhosis and up to 50% of patients with alcohol-related liver disease or Child-Pugh class C cirrhosis. Sarcopenia was independently associated with an ∼2-fold higher risk of mortality in patients with cirrhosis. The mortality rate increased with greater severity or longer durations of sarcopenia. Increasing awareness about the importance of sarcopenia in patients with cirrhosis among stakeholders must be prioritized.

Natural History and Hepatocellular Carcinoma Risk in Untreated Chronic Hepatitis B Patients With Indeterminate Phase.

BACKGROUND & AIMS: Many patients with chronic hepatitis B (CHB) may not conform to any of the defined phases and hence are classified as indeterminate. We aimed to characterize the baseline prevalence of indeterminate patients and their natural history, phase transition, and hepatocellular carcinoma (HCC) risk. METHODS: This was a retrospective cohort study of 3366 adult untreated noncirrhotic CHB patients seen at 5 US clinics and 7 Taiwanese townships who had at least 1 year of serial laboratory data before enrollment with a mean follow-up period of 12.5 years. Patients' clinical phases were determined at baseline and through serial data during follow-up evaluation, based on the American Association for the Study of Liver Diseases 2018 guidance. RESULTS: At baseline, 1303 (38.7%) patients were in the indeterminate phase. By up to year 10 of follow-up evaluation, 686 patients (52.7%) remained indeterminate, while 283 patients (21.7%) became immune active. Compared with patients who remained inactive, patients who remained indeterminate had a higher 10-year cumulative HCC incidence (4.6% vs 0.5%; P < .0001) and adjusted hazard ratio for HCC of 14.1 (P = .03). Among patients who remained indeterminate, age 45 years and older (adjusted hazard ratio, 18.4; P = .005) was associated independently with HCC development. CONCLUSIONS: Nearly 40% of patients had indeterminate CHB phase. Of these, half remained indeterminate and one-fifth transitioned to the immune active phase. HCC risk in persistently indeterminate CHB was 14 times higher than inactive CHB. Among persistently indeterminate CHB patients, age 45 years and older was associated with an 18 times higher risk for HCC development. Further studies are needed to evaluate the potential benefit of antiviral therapy for indeterminate patients, especially in the older subgroup.

2019 Global NAFLD Prevalence: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: The increasing rates of obesity and type 2 diabetes mellitus may lead to increased prevalence of nonalcoholic fatty liver disease (NAFLD). We aimed to determine the current and recent trends on the global and regional prevalence of NAFLD. METHODS: Systematic search from inception to March 26, 2020 was performed without language restrictions. Two authors independently performed screening and data extraction. We performed meta-regression to determine trends in NAFLD prevalence. RESULTS: We identified 17,244 articles from literature search and included 245 eligible studies involving 5,399,254 individuals. The pooled global prevalence of NAFLD was 29.8% (95% confidence interval [CI], 28.6%-31.1%); of these, 82.5% of included articles used ultrasound to diagnose NAFLD, with prevalence of 30.6% (95% CI, 29.2%-32.0%). South America (3 studies, 5716 individuals) and North America (4 studies, 18,236 individuals) had the highest NAFLD prevalence at 35.7% (95% CI, 34.0%-37.5%) and 35.3% (95% CI, 25.4%-45.9%), respectively. From 1991 to 2019, trend analysis showed NAFLD increased from 21.9% to 37.3% (yearly increase of 0.7%, P < .0001), with South America showing the most rapid change of 2.7% per year, followed by Europe at 1.1%. CONCLUSIONS: Despite regional variation, the global prevalence of NAFLD is increasing overall. Policy makers must work toward reversing the current trends by increasing awareness of NAFLD and promoting healthy lifestyle environments.

Clinical Profiles of Asians with NAFLD: A Systematic Review and Meta-Analysis.

INTRODUCTION: NAFLD is increasingly prevalent in Asia, where people suffer more metabolic comorbidities at a lower body mass index (BMI), suggesting potential differences in their clinical profile. Therefore, we attempted to characterize the clinical profile of Asians with NAFLD via a meta-analytic approach. METHODS: We searched PubMed, EMBASE, and Cochrane databases from January 1, 2000, to January 17, 2019. Two authors independently reviewed and selected 104 articles (2,247,754 persons) that identified NAFLD in Asians and reported relevant data, especially BMI and ALT, and excluded individuals with other liver disease and excessive alcohol consumption. Individual patient-level data were obtained from seven cohorts in Asia to complement meta-analyzed data. RESULTS: Overall, the mean age was 52.07 (95% CI: 51.28-52.85) years, with those from Southeast Asia (42.66, 95% CI: 32.23-53.11) being significantly younger. The mean BMI was 26.2 kg/m2, higher in moderate-severe versus mild hepatic steatosis (28.3 vs. 25.7) patients and NFS ≥ -1.455 versus <-1.455 (27.09 vs. 26.02), with 34% having nonobese NAFLD. The mean ALT was 31.74 U/L, higher in NFS < -1.455 versus ≥-1.455 (33.74 vs. 27.83), though no differences were found by obesity or steatosis severity. The majority of males (85.7%) and females (60.7%) had normal to minimally elevated ALT (1-1.5 × 95% ULN). Individual patient-level data analysis (N = 7,668) demonstrated similar results. CONCLUSION: About one-third of Asians with NAFLD were nonobese, and the majority did not have markedly elevated ALT. Therefore, abnormal ALT or BMI is not recommended as a criterion for NAFLD screening in this population. Additionally, there were significant differences in the clinical profiles of NAFLD among the different regions of Asia.