ObjectiveThe aim of the study is to identify the impact of postacute SARS-CoV-2 infection on patient outcomes.DesignThis is a prospective, repeated measure, observational study of consented adults with positive SARS-CoV-2 quantitative polymerase chain reaction or antigen test more than 28 days after infection. Only data from the initial study visit are reported, including disease history, symptoms checklist, patient questionnaires, cognitive tests, social/medical histories, vitals, grip strength, and 2-min walk distance.ResultsTwo hundred eighteen patients were studied: 100 hospitalized (57.3 +/- 15.4 yrs, 62% male, body mass index: 31.3 +/- 8.0) and 118 nonhospitalized (46.2 +/- 14.6 yrs, 31% male, body mass index: 29.7 +/- 7.5). Post-COVID patients reported mean 1.76 symptoms; >= 15% reported fatigue, memory loss, and shortness of breath. Grip strength was 14% lower than norms (P < 0.0001). Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue), mood (Patient Health Questionnaire), and well-being (EuroQol 5 Dimension 5 Level) scores were lower than the population norms (P < 0.05). Hospitalized versus nonhospitalized post-COVID patients performed worse on cognitive assessments (processing speed test-Wechsler Adult Intelligence Scale-Fourth Edition Symbol Search) and reported less regular exercise (>= 30 mins >= 3x per week; P < 0.05). In addition, 30% had severe fatigue (by the Functional Assessment of Chronic Illness Therapy-Fatigue); those patients reported less exercise (P < 0.05). In multivariate models, lack of exercise was independently associated with multiple post-COVID-19 impairments.ConclusionsLow levels of exercise are an independent risk factor for post-COVID sequelae. Patients who report less exercise have low grip strength, higher levels of fatigue, memory loss, shortness of breath, depression, and poorer quality of life.

SummaryBackgroundThe presence of fibrosis in NAFLD is the most significant risk factor for adverse outcomes. We determined the cutoff scores of two non‐invasive te sts (NITs) to rule in and rule out significant fibrosis among NAFLD patients.MethodsClinical data and liver biopsies were used for NAFLD patients included in this analysis (2001–2020). The enhanced liver fibrosis (ELF) and FIB‐4 NITs were calculated. Liver biopsies were read by a single hematopathologist and scored by the NASH CRN criteria. Significant fibrosis was defined as stage F2–F4.ResultsThere were 463 NAFLD patients included: 48 ± 13 years old, 31% male, 35% type 2 diabetes; 39% had significant fibrosis; mean ELF score was 9.0 ± 1.2, mean FIB‐4 score was 1.22 ± 1.05. Patients with significant fibrosis were older, more commonly male, had lower BMI but more components of metabolic syndrome, higher ELF and FIB‐4 (p < 0.0001). The performance of the two NITs in identifying significant fibrosis was: AUC (95% CI) = 0.78 (0.74–0.82) for ELF, 0.79 (0.75–0.83) for FIB‐4. The combination of ELF score ≥9.8 and FIB‐4 ≥ 1.96 returned a positive predictive value of 95% which can reliably rule in significant fibrosis (sensitivity 22%, specificity >99%), while an ELF score ≤7.7 or FIB‐4 ≤ 0.30 had a negative predictive value of 95% ruling out significant fibrosis (sensitivity 98%, specificity 22%).ConclusionsThe combination of ELF and FIB‐4 may provide practitioners with easily obtained information to risk stratify patients with NAFLD who could be referred to specialists or for enrollment in clinical trials.

BACKGROUND & AIMS: Cardiovascular disease is the most common cause of death among patients with nonalcoholic fatty liver disease (NAFLD). We assessed select cardiac biomarker associations for existing or future coronary artery disease (CAD) risk in patients with NAFLD. METHODS: Patients with/without NAFLD undergoing elective cardiac angiography were prospectively enrolled. Severe CAD was defined as presence of at least 1 proximal artery >70% stenosis; risk of severe CAD as either existing severe CAD or atherosclerotic cardiovascular disease score >= 20; NAFLD was defined as hepatic fat in the absence of other liver diseases. Cardiac biomarkers (high-sensitivity C-reactive protein, N-terminal pro-brain natriuretic peptide, and high-sensitivity cardiac troponin I [hs-cTnI]) were measured using Atellica Solution assays (Siemens Healthineers). RESULTS: A total of 619 patients were enrolled (mean age, 63 +/- 10 years; 80% male; 31% type 2 diabetes; 65% NAFLD); 42% had severe CAD, and 57% had risk of severe CAD. NAFLD prevalence was similar between patients with and without severe CAD (68% vs 62%; P > .05). Patients with NAFLD with severe CAD (44%) or with risk of severe CAD (58%) had higher levels of hscTnI than NAFLD controls (both P < .001). Presence of severe CAD or risk of severe CAD in all patients was associated with older age, male, aspects of metabolic syndrome, and elevated hscTnI: odds ratio 2.0 (95% confidence interval [CI],1.4-2.9) and 1.8 (95% CI, 1.1-3.0), respectively; 2.3 (95% CI, 1.4-3.8) and 2.2 (95% CI, 1.2-4.2), respectively, in patients with NAFLD (all P < .02). CONCLUSION: CAD is common in patients with NAFLD. High hs-cTnI was associated with an increased risk of CAD. Pending validation, hs-cTnI may be a useful marker for CAD risk prediction in patients with NAFLD.

Abstract Patients with preexisting chronic liver disease (CLD) may experience a substantial burden from both coronavirus 2019 (COVID‐19) infection and pandemic‐related life disruption. We assessed the impact of the COVID‐19 pandemic on patients with CLD. Patients enrolled in our Global Liver Registry were invited to complete a COVID‐19 survey. As of June 2021, 2500 patients (mean age ± SD, 49 ± 13 years; 53% men) from seven countries completed the survey. Of all survey completers, 9.3% had COVID‐19. Of these patients, 19% were hospitalized, 13% needed oxygen support, but none required mechanical ventilation. Of all patients including those not infected with COVID‐19, 11.3% reported that the pandemic had an impact on their liver disease, with 73% of those reporting delays in follow‐up care. The Life Disruption Event Perception questionnaire confirmed worsening in at least one area (food/nutrition, exercise, social life, vocation/education, financial situation, housing, or health care) in 81% and 69% of patients with and without a history of COVID‐19, respectively (p = 0.0001). On a self‐assessed Likert health score scale (range, 1–10; 10 indicates perfect health), patients with a COVID‐19 history scored lower (mean ± SD, 6.7 ± 2.2 vs. 7.4 ± 2.2, respectively; p < 0.0001) despite reporting similar health scores if there was no pandemic (mean ± SD, 8.5 ± 1.4 vs. 8.4 ± 1.6, respectively; p = 0.59). After adjustment for country of enrollment, liver disease etiology and severity, age, sex, body mass index, diabetes, and history of psychiatric comorbidities, COVID‐19 was found to be independently associated with lower self‐assessed health scores (beta = −0.71 ± 0.14; p < 0.0001). The COVID‐19 pandemic resulted in a substantial burden on the daily life of patients with CLD.

Abstract Background COVID-19 outcomes among hospitalized patients may have changed due to new variants, therapies and vaccine availability. We assessed outcomes of adults hospitalized with COVID-19 from March 2020–February 2022. Methods Data were retrieved from electronic health medical records of adult COVID-19 patients hospitalized in a large community health system. Duration was split into March 2020–June 2021 (pre-Delta period), July–November 2021 (Delta period), and December 2021–February 2022 (Omicron period). Results Of included patients (n = 9582), 75% were admitted during pre-Delta, 9% during Delta, 16% during Omicron period. The COVID-positive inpatients were oldest during Omicron period but had lowest rates of COVID pneumonia and resource utilization (p < 0.0001); 46% were vaccinated during Delta and 61% during Omicron period (p < 0.0001). After adjustment for demographics and comorbidities, vaccination was associated with lower inpatient mortality (OR = 0.47 (0.34–0.65), p < 0.0001). The Omicron period was independently associated with lower risk of inpatient mortality (OR = 0.61 (0.45–0.82), p = 0.0010). Vaccination and Omicron period admission were also independently associated with lower healthcare resource utilization (p < 0.05). Magnitudes of associations varied between age groups with strongest protective effects seen in younger patients. Conclusion Outcomes of COVID-19 inpatients were evolving throughout the pandemic and were affected by changing demographics, virus variants, and vaccination. Key point In this observational study of almost 10,000 patients hospitalized from March 2020–February 2022 with COVID-19, age and having multiple comorbidities remained consistent risk factors for mortality regardless of the variant. Vaccination was high in our hospitalized patients. Vaccination conveyed less severe illness and was associated with lower inpatient mortality.

Background: Patients with nonalcoholic fatty liver disease (NAFLD) and fibrosis stage ≥ 2 (F2-F4) are at risk for adverse outcomes and considered to be candidates for clinical trials. We aimed to use two NITs combined to rule in and rule out fibrosis stages F2-F4 among patients with NAFLD. Methods: Data were collected from patients with NAFLD diagnosis. The Enhanced Liver Fibrosis (ELF) and FIB-4 NITs were calculated. Liver biopsies were read by 1 hepatologist; scored by NASH CRN criteria. Significant fibrosis stage was ≥ F2, advanced fibrosis was ≥ F3. Results: There were 463 NAFLD patients: 48±13 years old, 31% male, 35% type 2 diabetes, 39% had significant fibrosis and 24% advanced fibrosis. In comparison to those without significant fibrosis, patients with significant fibrosis were older (mean age 52 vs. 45 years) , more commonly male (38% vs. 26%) , and had more components of metabolic syndrome (type 2 diabetes, hypertension, hyperlipidemia) as well as higher ELF and FIB-4 scores; similar trends were observed for patients with vs. without advanced fibrosis (p<0.05) . The performance of the two NITs in identifying NAFLD patients with significant fibrosis was as follows: AUC (95% CI) = 0.78 (0.74-0.82) for ELF, 0.79 (0.75-0.83) for FIB-4; for advanced fibrosis AUC = 0.81 (0.77-0.85) for ELF, 0.83 (0.79 - 0.86) for FIB-4. A combination of ELF score ≥9.8 and FIB-4 ≥1.96 returned PPV of 95% which can reliably rule in significant fibrosis (sensitivity 22%, specificity >99%) , while an ELF score ≥7.7 and FIB-4 ≥0.30 had NPV of 95% which can be used to rule out significant fibrosis (sensitivity 98%, specificity 22%) . For advanced fibrosis, similar rules were ELF ≥9.8 and FIB-4 ≥2.90 (PPV 95%, sensitivity 18%, specificity >99%) to rule in; ELF ≥7.2 and FIB-4 ≥0.74 (NPV 95%, sensitivity 92%, specificity 49%) to rule out. Conclusions: The combination of ELF and FIB-4 can provide an easy algorithm with high predictive value to detect significant or advanced fibrosis in NAFLD. Disclosure Z.Younossi: Consultant; Bristol-Myers Squibb Company, Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Quest Diagnostics, Siemens. S.Felix: None. T.Jeffers: Stock/Shareholder; Neurometrix. E.Younossi: None. F.Nader: None. A.Racila: None. B.P.Lam: Consultant; Intercept Pharmaceuticals, Inc. M.Stepanova: None.

BACKGROUND AND AIMS:Nonalcoholic fatty liver disease (NAFLD) subjects with fibrosis stage ≥2 are at high risk for mortality. We aimed to provide national estimates and temporal trends for NAFLD, based on different fibrosis severity. METHODS:Data from the National Health and Nutrition Examination Survey (NHANES) (1999-2016) and NHANES III (1988-1994) were utilized. NAFLD was determined by ultrasound showing moderate to severe steatosis. For those without ultrasound, NAFLD was determined by the U.S. Fatty Liver Index score of ≥30. Hepatic fibrosis was assessed using Fibrosis-4 (FIB-4) score (FIB-4 <1.3 = low risk; FIB-4 1.3-2.67 = moderate risk; and FIB-4 >2.67 = high risk). Annual percent change (APC) was calculated by using the joinpoint regression model. RESULTS:From NHANES III, 10,854 individuals were included (mean age 43.5 years; 47.5% male; 75.7% non-Hispanic White) and 37.7% had NAFLD. Among them, based on FIB-4, 80% had low-risk, 18.6% had moderate-risk, and 1.4% had high-risk NAFLD. NAFLD with moderate or high risk was more likely to have hypertension, hyperlipidemia, diabetes, cardiovascular disease, and metabolic syndrome than was low-risk NAFLD (all P < .02). NAFLD prevalence increased from 29.5% in 1999-2000 to 40.3% in 2015-2016 (APC, 2.78%; P < .02), moderate-risk NAFLD increased from 6.26% to 14.17% (APC, 5.34%; P < .02), and high-risk NAFLD increased from 0.49% to 1.15% (APC, 9.72%; P < .02). Independent predictors of advanced fibrosis were age (OR, 1.11; 95% CI, 1.06-1.17; P = .001) and diabetes (OR, 2.28; 95% CI, 1.03-5.05; P = .04). Compared with low-risk NAFLD, high-risk NAFLD was associated with significantly increased all-cause (HR, 1.53; 95% CI, 1.09-2.15; P = .01), cardiovascular disease-specific (HR, 1.99; 95% CI, 1.22-3.24, P < .01) and liver-specific (HR, 4.57; 95% CI, 1.03-28.79; P = .04) mortality. CONCLUSIONS:The prevalence of moderate- or high-risk NAFLD is increasing and is associated with increased all-cause, liver-related, and cardiovascular mortality.

INTRODUCTION: We aimed to identify high-risk nonalcoholic fatty liver disease (NAFLD) patients seen at the primary care and endocrinology practices and link them to gastrohepatology care. METHODS: Using the electronic health record, patients who either had the diagnosis of type 2 diabetes or had 2 of 3 other metabolic risk factors met criteria for inclusion in the study. Using noninvasive fibrosis tests (NITs) to identify high risk of fibrosis, patients who met the NIT prespecified criteria were referred to gastrohepatology for clinical assessment and transient elastography. RESULTS: From 7,555 patients initially screened, 1707 (22.6%) met the inclusion criteria, 716 (42%) agreed to enroll, and 184 (25.7%) met the prespecified NIT criteria and eligibility for linkage to GE-HEP where 103 patients (68 ± 9 years of age, 50% men, 56% white) agreed to undergo linkage assessments. Their NIT scores were APRI of 0.38 ± 0.24, FIB-4 of 1.98 ± 0.87, and NAFLD Fibrosis Score of 0.36 ± 1.03; 68 (66%) linked patients had controlled attenuation parameter >248 dB/m, 62 (60%) had liver stiffness <6 kPa, and 8 (8%) had liver stiffness >12 kPa. Liver stiffness for the overall group was 6.7 ± 4.2 kPa, controlled attenuation parameter 282 ± 64 dB/m, and FAST score 0.22 ± 0.22. Linked patients with presumed advanced fibrosis had significantly higher body mass index (36.4 ± 6.6 vs 31.2 ± 6.4 kg/m2, P = 0.025) and higher NIT scores (APRI 0.89 ± 0.52 vs 0.33 ± 0.14, FIB-4 3.21 ± 2.06 vs 1.88 ± 0.60, and NAFLD Fibrosis Score 1.58 ± 1.33 vs 0.25 ± 0.94). DISCUSSION: By applying a simple prespecified multistep algorithm using electronic health record with clinical risk factors and NITs followed by transient elastography, patients with nonalcoholic fatty liver disease seen in PCP and ENDO practices can be easily identified.

IMPORTANCE The most important surrogate for increased risk of adverse clinical outcomes among patients with nonalcoholic fatty liver disease (NAFLD) is the patient's stage of liver fibrosis. There is a significant barrier to risk-stratifying patients in clinical practice owing to the need for liver biopsy. OBJECTIVE To determine the performance of the enhanced liver fibrosis (ELF) test as a noninvasive test for assessment of liver fibrosis among patients with NAFLD. DESIGN, SETTING, AND PARTICIPANTS This retrospective cross-sectional study was conducted among patients recruited from a large, community-based hospital system's outpatient liver clinic from 2001 to 2020. Patients with NAFLD defined as steatosis greater than 5% without evidence of other liver disease or excessive alcohol use were included. Data were analyzed from August 2020 through February 2021. INTERVENTION Enhanced liver fibrosis score was calculated. MAIN OUTCOMES AND MEASURES Advanced fibrosis was identified by liver biopsy or transient elastography. RESULTS Among 829 patients with NAFLD, the mean (SD) age was 53.1 (14.0) years, there were 363 (43.8%) men, 294 patients (35.5%) had type 2 diabetes, and the mean (SD) fibrosis-4 (fib-4) score was 1.34 (0.97). There were 463 patients with liver biopsy, among whom 113 individuals (24.4%) had bridging fibrosis or cirrhosis; among 462 patients with transient elastography data, 79 individuals (17.1%) had liver stiffness results of 9.6 kPa or more (ie, advanced fibrosis). Patients with advanced fibrosis had statistically significantly increased mean (SD) ELF scores compared with patients without advanced fibrosis as determined by biopsy (10.1 [1.3] vs 8.6 [1.0]; P < .001) or transient elastography (10.0 [1.1] vs 9.0 [0.8]; P < .001). Among all patients with NAFLD, the area under the receiver operating characteristic curve (AUROC) for ELF in identifying patients with advanced fibrosis was 0.81 (95% CI, 0.77-0.85) for patients diagnosed by biopsy and 0.79 (95% CI, 0.75-0.82) for those diagnosed by transient elastography. Performance of the ELF score was similar among patients with NAFLD who were aged 65 years or older (AUROC, 0.74; 95% CI, 0.58-0.87) or had type 2 diabetes (AUROC, 0.78; 95% CI, 0.71-0.84). The combination of an ELF score of 7.2 or greater with a fib-4 score of 0.74 or greater was associated with a negative predictive value of 95.1% (95% CI, 91.8%-98.4%) and a sensitivity of 92.5% (95% CI, 87.4%-97.5%), which can reliably rule out advanced fibrosis. An ELF score of 9.8 or greater with a fib-4 score of 2.9 or greater was associated with a positive predictive value of 95.0% (95% CI, 85.5%-100%) and a specificity of 99.7% (95% CI, 99.1%-100%), which can be used to rule in advanced fibrosis. CONCLUSIONS AND RELEVANCE These findings suggest that the ELF test performs well in identifying patients with NAFLD who are at increased risk of advanced fibrosis and that this test combined with fib-4 score may be reliably used in clinical practice to assess the presence or absence of advanced fibrosis among patients with NAFLD.

The impact of the coronavirus disease 2019 (COVID‐19) pandemic among patients with chronic liver disease is unknown. Given the high prevalence of nonalcoholic fatty liver disease (NAFLD), we determined the predictors of mortality and hospital resource use among patients with NAFLD admitted with COVID‐19 by using electronic medical records data for adult patients with COVID‐19 hospitalized in a multihospital health system who were discharged between March and December 2020. NAFLD was diagnosed by imaging or liver biopsy without other liver diseases. Charlson’s comorbidity index (CCI) and Elixhauser comorbidity index (ECI) scores were calculated. In the study sample, among the 4,835 patients hospitalized for COVID‐19, 553 had NAFLD (age: 55 ± 16 years, 51% male, 17% White, 11% Black, 58% Hispanic, 8% Asian, 5% from congregated living, 58% obese, 15% morbid obesity [body mass index ≥ 40], 51% type 2 diabetes, 63% hypertension, mean [SD] baseline CCI of 3.9 [3.2], and baseline ECI of 13.4 [11.3]). On admission, patients with NAFLD had more respiratory symptoms, higher body temperature and heart rate, higher alanine aminotransferase and aspartate aminotransferase than non‐NAFLD controls (n = 2,736; P < 0.05). Of the patients with NAFLD infected with COVID‐19, 3.9% experienced acute liver injury. The NAFLD group had significantly longer length of stay, intensive care unit use, and mechanical ventilation, with a crude inpatient mortality rate of 11%. In multivariate analysis, independent predictors of inpatient mortality among patients with NAFLD infected with COVID‐19 were older age, morbid obesity, ECI score ≥ 11, higher Fibrosis‐4 Index (FIB‐4) score, and oxygen saturation <90% (all P < 0.05), but not sex, race/ethnicity, or any individual comorbidity (all P > 0.05). Conclusion: Patients with NAFLD infected with COVID‐19 tend to be sicker on admission and require more hospital resource use. Independent predictors of mortality included higher FIB‐4 and multimorbidity scores, morbid obesity, older age, and hypoxemia on admission.