Severe, Persistent, Disruptive Fatigue Post-SARS-CoV-2 Disproportionately Affects Young Women.

Introduction: Post-acute SARS-CoV-2 (PASC) symptoms are often persistent, disruptive, and difficult to treat effectively. Fatigue is often among the most frequently reported symptoms and may indicate a more challenging road to recovery. Purpose: To describe the natural history, symptomology, and risk profile of long-term post-acute SARS-CoV-2. Patients and Methods: Participants treated for SARS-CoV-2 within a large, community health system in the US were enrolled prospectively in a longitudinal, observational PASC study examining participants at enrollment and 6 months. Medical history, symptom reporting, validated measures of cognition, and patient-reported outcomes (PROs), were performed for all participants and repeated during study follow-up visits. Results: A total of 323 participants completed baseline evaluations. Sixty one participants indicated clinically significant fatigue (23.1% at baseline); a representative sample of 141 enrollees also completed a baseline Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) in-depth fatigue reporting questionnaire, 37 had severe fatigue. The severely fatigued (FACIT-F ≤29.7) were significantly younger, female, had more anxiety and depression, had a higher resting heart rate, reported more sick days, and were less physically active post-COVID. They were more likely to have a diagnosis of chronic kidney disease (13.5% vs 2.9%) but less likely to have a history of cancer (8.1% vs 23.1). Participants who were severely fatigued reported health, diet, weight, and sleep were worse than those not severely fatigued post-COVID (p = 0.02 to 0.0002). Fatigue was significantly correlated with impairment of all PROs administered after COVID-19 infection. Conclusion: Fatigue is a common symptom post-COVID-19 infection and is associated with lower reported well-being and function. Those with severe fatigue tended to be younger and female and have a past medical history of anxiety, depression, kidney disease, and more sedentary lifestyles.

Post-Acute SARS-CoV-2 Symptoms are Fewer, Less Intense Over Time in People Treated with Mono-Clonal Antibodies for Acute Infection.

Introduction: Many with post-acute SARS-CoV-2 (PASC) have persistent symptoms impacting physical and cognitive function, decreased health and health-related life quality. Monoclonal antibody (mAb) treatment was available to acutely infected patients which might improve these outcomes. Purpose: To compare patient perception of PASC symptoms for those receiving bamlanivimab or casirivimab and imdevimab (mAbs) to those not receiving this treatment (non-mAbs). To compare changes between these groups in symptoms, function and quality of life over a 6-month follow-up. Patients and Methods: Consented adults >28 days post-infection with positive SARS-CoV-2 qPCR or antigen test and SARS-CoV-2 infection between March of 2020 and July of 2022 were enrolled. This prospective, repeated measure observational study reports baseline through 6-month follow-up. Extensive sociodemographic data, detailed medical history, COVID-19 symptom history, and standardized measures of well-being, depression, anxiety, stigma, cognition, symptom assessment, distress, and health status were collected. Results: 323 participants [101 mAb, 221 non-mAb, 52.7±15.5 years, 47.7% male, body mass index (BMI) 31.4±8.4] were analyzed. Fewer symptoms at baseline were reported in mAb versus non-mAb participants (1.06±1.31 vs 1.78±2.15, respectively p=0.0177) 6 months: (0.911±1.276 mAb vs.1.75±2.22 non-mAb, p=0.0427). Both groups showed significant within-group decreases in symptom number (52 to 21 mAb, 126 to 63 non-mAb) and symptom burden (p=0.0088 mAb, p<0.00001 non-mAb). mAb patients had significantly shorter infection-to-baseline interval (days) (120.4±55.3 mAb vs 194.0±89.3 non-mAb, p<0.00001); less frequent history of myocardial infarction (0.0 vs 3.9%, p=0.0464); headache (2.0% vs.11.8%, p=0.0046), rash (3.1% vs 9.9%, p=0.0377), and miscellaneous muscle complaints (2.0% vs 12.3%, p=0.0035), plus significantly better 6-month mood. (2.2% vs 13.2%, p=0.0390). Conclusion: mAb treated participants had reduced symptom burden and consistently reported fewer symptoms than non-mAb at all time points despite less time since acute illness. Both groups reported a statistically significant decrease in symptoms by 6-month visit with no statistically significant differences between them at follow-up.

Association of physical activity and fine motor performance in individuals with type 2 diabetes mellitus and/or non-alcoholic fatty liver disease.

BACKGROUND: Fine motor performance may serve as an early warning sign for reduced cognitive function. Physical activity can help preserve cognitive function; however, the relationship between fine motor performance and physical activity is not well understood. Therefore, this study examined the relationship between fine motor performance and physical activity in individuals at risk for developing cognitive impairment (those with diabetes and/or non-alcoholic fatty liver disease (NAFLD)). PATIENTS AND METHODS: Individuals aged 25-69 with and without diabetes and NAFLD were enrolled. For this cross-sectional study, all participants completed the Human Activity Profile and fine motor performance tasks (Grooved Pegboard Test and Trail Making Test). RESULTS: There were 93 participants in the study (NAFLD only (n = 29); diabetes + NAFLD (n = 34), controls (n = 30)). Individuals with both diabetes and NAFLD were less physically active and performed slower on the fine motor performance task. A statistically significant correlation was found between physical activity and motor speed among those with NAFLD only (r = 0.436, p<.05), which remained statistically significant after controlling for body mass index (r = 0.385; p<.05). CONCLUSIONS: This study suggests that those with diabetes + NAFLD have lower levels of physical activity and slower fine motor performance. The relationship between physical activity and fine motor performance was only statistically significant in the group of individuals with NAFLD only. Future research needs to explore the mechanisms that impact fine motor performance and physical activity in individuals at risk for mild cognitive impairment. Individuals with diabetes and/or NAFLD should be identified, advised and encouraged to engage in physical activity.Key MessagesThose with NAFLD and T2DM have lower levels of physical activity and slower fine motor performance compared to controls and those with NAFLD only.Future research needs to explore the mechanisms that impact fine motor performance and physical activity in those with T2DM with or without NAFLD.Individuals with impaired fine motor performance should be identified and encouraged to engage in physical activity.

Regular Exercise Is Associated With Low Fatigue Levels and Good Functional Outcomes After COVID-19: A Prospective Observational Study.

OBJECTIVE: The aim of the study is to identify the impact of postacute SARS-CoV-2 infection on patient outcomes. DESIGN: This 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. RESULTS: Two 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 ≥3× 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. CONCLUSIONS: Low 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.

Nonalcoholic Fatty Liver Disease Is Independently Associated With Higher All-Cause and Cause-Specific Mortality.

BACKGROUND & AIMS: The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing globally. We assessed independent associations of NAFLD with all-cause and cause-specific mortality in older community-dwelling adults in the United States. METHODS: Data from the Rancho Bernardo Study cohort, who participated in the research from 1992 to 1996 with mortality data (followed up to July 2019), were analyzed. NAFLD was determined by the improved Fatty Liver Index for the multiethnic US population in the absence of secondary causes of liver disease. Hazard ratios (HRs), 95% CIs, and population-attributable fractions of risk factors on mortality were calculated. Competing-risk analyses of cause-specific mortality were performed. RESULTS: Of the 1523 eligible participants (mean age, 71.8 y; 39.9% male; 99.3% non-Hispanic White; and 10.7% obese), 404 (26.4%) had NAFLD. During 23,311 person-years of follow-up evaluation (mean, 15.22 y; SD, 8.41 y), among NAFLD and non-NAFLD, there were 296 and 717 deaths from all causes, 113 and 263 cardiac deaths, 62 and 112 cancer deaths, and 6 and 2 liver deaths, respectively. NAFLD had a 26% higher all-cause mortality (HR, 1.26; 95% CI, 1.08-1.47) and a 33% (HR, 1.33; 95% CI, 1.04-1.70) and 55% (HR, 1.55; 95% CI, 1.11-2.15) higher cardiac and cancer mortality, respectively, than non-NAFLD. Population-attributable fractions showed 13.9% of deaths, 6.2% of cardiac deaths, and 12.1% of cancer deaths were attributable to NAFLD after adjustments of risk factors (sedentary lifestyle, obesity, hypertension, hyperlipidemia, diabetes). CONCLUSIONS: NAFLD is associated independently with all-cause, cardiac, and cancer mortality. Efforts must continue to raise awareness about NAFLD and develop care pathways and public health efforts to reduce NAFLD burden and associated mortality.

Second victim experiences and moral injury as predictors of hospitalist burnout before and during the COVID-19 pandemic.

BACKGROUND: The increasing number of physicians leaving practice, especially hospitalists, has been well-documented. The most commonly examined factor associated with this exodus has been burnout. The COVID-19 pandemic has put a unique and unprecedented stress on hospitalists who have been at the front lines of patient care. Therefore, the investigation of burnout and its related factors in hospitalists is essential to preventing future physician shortages. OBJECTIVE: This study examined the relationship between burnout, second victim, and moral injury experiences before and during the COVID-19 pandemic among hospitalists. METHODS: Two anonymous cross-sectional surveys of hospitalists from a community hospital in the metropolitan Washington, DC area were conducted. One was conducted pre-COVID-19 (September-November 2019) and one was conducted during COVID-19 (July-August 2020). The surveys were sent to all full-time hospitalists via an online survey platform. A variety of areas were assessed including demographic (e.g., age, gender), work information (e.g., hours per week, years of experience), burnout, second victim experiences, well-being, and moral injury. RESULTS: Burnout rates among providers during these two time periods were similar. Second victim experiences remained prevalent in those who experienced burnout both pre and during COVID-19, but interestingly the prevalence increased in those without burnout during COVID-19. Moral injury was predictive of burnout during COVID-19. CONCLUSION: While there were some factors that predicted burnout that were similar both pre- and during-pandemic, moral injury was unique to predicting burnout during COVID-19. With burnout as a contributing factor to future physician shortages, it is imperative that predictive factors in a variety of different environments are well understood to prevent future shortages. Hospitalists may be an excellent barometer of these factors given their presence on the front line during the pandemic, and their experiences need to be further explored so that targeted interventions aimed at addressing those factors may be created.

The impact of variants and vaccination on the mortality and resource utilization of hospitalized patients with COVID-19.

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.

Interrelationship between physical activity and depression in nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is associated with a sedentary lifestyle and depressive symptoms. It is also well established that physical inactivity and depressive symptoms are related. However, an investigation of the interaction between all of these factors in NAFLD has not been previously conducted. AIM: To investigate the interrelationship between physical inactivity and depressive symptoms in individuals with NAFLD. METHODS: Data from the Rancho Bernardo Study of Healthy Aging were utilized. 589 individuals were included in the analyses (43.1% male; 95.8% non-Hispanic white; aged 60.0 ± 7.0 years). NAFLD was defined by using the hepatic steatosis index, depression using the Beck Depression Inventory, and physical activity by self-report of number of times per week of strenuous activity. Multivariable generalized linear regression models with Gamma distribution were performed to investigate the proposed relationship. RESULTS: About 40% of the sample had evidence of NAFLD, 9.3% had evidence of depression, and 29% were physically inactive. Individuals with NAFLD and depression were more likely to be physically inactive (60.7%) compared to individuals with neither NAFLD nor depression (22.9%), individuals with depression without NAFLD (37.0%), and individuals with NAFLD without depression (33.3%). After accounting for various comorbidities (i.e., age, sex, diabetes, hypertension, obesity), individuals with NAFLD and higher levels of physical activity were at a decreased odds of having depressive symptoms [16.1% reduction (95% confidence interval: -25.6 to -5.4%), P = 0.004], which was not observed in those without NAFLD. CONCLUSION: Individuals with NAFLD have high levels of physical inactivity, particularly those with depressive symptoms. Because this group is at high risk for poor outcomes, practitioners should screen for the coexistence of depressive symptoms and NAFLD. This group should receive appropriate interventions aimed at increasing both participation and levels of intensity of physical activity.

Independent Predictors of Mortality Among Patients With NAFLD Hospitalized With COVID-19 Infection.

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.

Causes of death in patients with Non-alcoholic Fatty Liver Disease (NAFLD), alcoholic liver disease and chronic viral Hepatitis B and C.

INTRODUCTION AND OBJECTIVES: Cause of mortality in patients with chronic liver diseases (CLDs) may differ based on underlying etiology of liver disease. Our aim was to assess different causes of death in patients with the most common types of CLD using a national database from the United States. MATERIALS AND METHODS: Death data from 2008 and 2018 from the National Vital Statistics System (NVSS) by the National Center for Health Statistics (NCHS) were used. The rank of cause-of-death for each etiology of CLDs was assessed. Causes of death were classified by the ICD-10 codes. Liver-related deaths included liver cancer, cirrhosis and CLDs. RESULTS: Among a total of 2,826,531 deaths in 2018, there were 85,807 (3.04%) with underlying CLD (mean age at death 63.0 years, 63.8% male, 70.8% white). Liver-related mortality was the leading cause of death for all types of CLD [45.8% in non-alcoholic fatty liver disease (NAFLD), 53.0% in chronic hepatitis C (CHC), 57.8% in chronic hepatitis B (CHB), 81.8% in alcoholic liver disease (ALD)]. This was followed by death from cardiac causes (NAFLD 10.3%, CHC 9.1%, CHB 4.6%, ALD 4.2%) and extrahepatic cancer (NAFLD 7.0%, CHC 11.9%, CHB 14.9%, ALD 2.1%). Although liver cancer was the leading cause of cancer death, lung, colorectal and pancreatic cancer were also common causes of cancer death. CONCLUSIONS: Among deceased patients with CLD, underlying liver disease was the leading cause of death. Among solid cancers, liver cancer was the leading cause of cancer-related mortality.

Hospice care utilisation among elderly patients who died with hepatocellular carcinoma in the United States.

BACKGROUND & AIMS: The benefits of hospice care in Medicare recipients with hepatocellular carcinoma (HCC) have not been fully evaluated, which we aimed to study. METHODS: We used nationally representative samples of the Medicare beneficiaries in the USA (2011-2016) to assess the impact of hospice care on the outcomes of patients with HCC. Hospice care benefits on the survival time, length of stay (LOS), 30-day readmissions, and daily charges during the last year and month of life were assessed by logistic regression and generalised linear regression. RESULTS: Among 2,230 Medicare beneficiaries with HCC (mean age, 74.9 years; non-Hispanic White 79.1%; male 66.6%), median survival from HCC diagnosis was 68 days; 556 (24.9%) received hospice services; median hospice LOS was 12 days (4-35 days). Hospice users increased from 20.1% to 31.1% over time, driven by enrolment ≤15 days (45.1-59.2%, respectively). In the last year of life, hospice users (vs. no hospice care) had longer median survival time (76.5 vs. 66 days), lower in-hospital mortality (1.1% vs. 25.5%) and lower median daily charges ($951 vs. $1,004) despite more inpatient admissions and higher comorbid diseases. Hospice enrolment was associated with 48.6% reduction in daily charges (95% CI: -54.9% to -41.5%). Longer hospice LOS was associated with lower rates of healthcare utilisation. Patients with chronic liver disease were less likely to enrol in hospice care (odds ratio = 0.18, 95% CI: 0.14-0.24). CONCLUSIONS: Although hospice provides a significant decrease in healthcare utilisation and some benefit in survival, most care is given in the last 2 weeks of life. Efforts to encourage earlier use of hospice services must continue. LAY SUMMARY: The purpose of hospice care is to provide comfort and lessen suffering at the end of life. Hospice care allows one to die outside the hospital environment which is the wish of most people. However, we found that among persons aged 65 years and older who were diagnosed with liver cancer (which has a poor prognosis), only 25% were enrolled in hospice care and the majority used a hospice only in the last weeks of life. This is a disheartening finding as liver cancer patients with longer hospice enrolment had lower costs and improved survival. We suggest that healthcare practitioners consider discussion of palliative and hospice care routinely with patients suffering from liver cancer.

Contribution of sarcopenia and physical inactivity to mortality in people with non-alcoholic fatty liver disease.

BACKGROUND & AIMS: Physical inactivity and sedentary lifestyle have contributed to the epidemic of obesity and non-alcoholic fatty liver disease (NAFLD). We assessed the association between physical activity, NAFLD, and sarcopenia, and their contributions to mortality. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) 1999-2004 with Linked Mortality file (through 2015) was utilised. NAFLD was determined by the US Fatty Liver Index in the absence of secondary causes of liver disease. Sarcopenia was defined using appendicular lean mass divided by body mass index by the Foundation for the National Institutes of Health criteria. Activity level was determined using standard self-reports. Publicly available imputed dual-energy X-ray absorptiometry data sets were used. RESULTS: Of 4,611 NHANES participants (48.2% males; 72.5% White; mean age 45.9 years), NAFLD was present in 1,351 (29.3%), of whom 17.7% had sarcopenia. Of the NAFLD group, 46.3% was inactive, whilst intermediate and ideal physical activity rates were observed in 14.2% and 39.5%, respectively. Sarcopenia was significantly and inversely related to higher physical activity level, both amongst NAFLD (odds ratio [OR] = 0.45 [95% CI 0.30-0.69]) and non-NAFLD (OR = 0.51 [0.35-0.75]) groups. During a median follow-up of 13.5 years, a total of 586 subjects died, of whom 251 had NAFLD. Amongst those who died with NAFLD, 33.0% had sarcopenia and 54.3% were inactive. Compared with NAFLD without sarcopenia, NAFLD with sarcopenia was associated with a higher risk of all-cause (hazard ratio [HR] = 1.78 [1.16-2.73]), cardiac-specific (HR = 3.19 [1.17-8.74]), and cancer-specific mortality (HR = 2.12 [1.08-4.15]). CONCLUSIONS: Inactivity is associated with presence of sarcopenia, whilst sarcopenia is associated with increased mortality amongst NAFLD patients. Sarcopenia should be a part of clinical assessment of patients with NAFLD. Treatment of NAFLD should include optimal management of sarcopenia. LAY SUMMARY: Nonalcoholic fatty liver disease (NAFLD) and sarcopenia have similar pathophysiological profiles. Our data show that sarcopenia is associated with inactivity in subjects with NAFLD. The presence of sarcopenia in patients with NAFLD poses increased risk for all-cause and cardiac-specific mortality.

Outcomes of Liver Transplant Candidates with Primary Biliary Cholangitis: The Data from the Scientific Registry of Transplant Recipients.

BACKGROUND: Primary biliary cholangitis (PBC) is progressive and can cause end-stage liver disease necessitating a liver transplant (LT). PBC patients may be disadvantaged on LT waitlist due to MELD-based priority listing or other factors. AIM: The aim was to assess waitlist duration, waitlist mortality, and post-LT outcomes of PBC patients. METHODS: The Scientific Registry of Transplant Recipients data for 1994-2016 was utilized. Adult patients with PBC without hepatocellular carcinoma (HCC) were selected. Their clinico-demographic parameters and waitlist and post-transplant outcomes were compared to those of patients with hepatitis C (HCV) without HCC. RESULTS: Out of 223,391 listings for LT in 1994-2016, 8133 (3.6%) was for PBC without HCC. Mean age was 55.5 years, 76.9% white, 86.2% female, mean MELD score 21, 6.6% retransplants. There were 52,017 patients with hepatitis C included for comparison. The mean waitlist mortality was 17.9% for PBC and 17.6% for HCV (p > 0.05). The average transplantation rate was 57.7% for PBC and 53.3% for HCV (p < 0.0001), while waitlist dropout (death or removal due to deterioration) rate was 25.0% for PBC and 25.4% for HCV (p > 0.05). There was no significant difference in median waiting duration till transplantation between PBC patients and HCV after 2002 (103 vs. 95 days, p > 0.05). Post-LT mortality and graft loss rates were significantly lower in PBC than in HCV patients (all p < 0.02). CONCLUSIONS: Despite no evidence of impaired waitlist outcomes and favorable post-transplant survival in patients with PBC, there is still a high waitlist dropout rate suggesting the presence of an unmet need for effective treatment.

Mortality Related to Nonalcoholic Fatty Liver Disease Is Increasing in the United States.

Population-level nonalcoholic fatty liver disease (NAFLD) death rate data are sparse. We described death rates for adults with NAFLD in the United States using mortality data from the National Vital Statistics System multiple-cause mortality data (2007-2016). Decedents who had NAFLD were identified by International Classification of Diseases (ICD) codes K75.81, K76.0, K74.0, K74.6, and K76.9. Among NAFLD decedents, cause-specific deaths (e.g., cardiovascular disease [CVD], cirrhosis, hepatocellular carcinoma [HCC], non-liver cancer, diabetes mellitus [DM]) were identified by underlying cause of death ICD-10 codes. Trends were evaluated by average annual percentage change (AAPC) in age-standardized death rate (ASDR) per 100,000 persons. Among the 25,129,960 decedents aged ≥20 years, 353,234 (1.4%) decedents had NAFLD (212,322 men; 260,765 non-Hispanic whites, 32,868 non-Hispanic blacks, 46,530 Hispanics, 5,025 non-Hispanic American Indian or Alaska Natives [AIANs], 7,023 non-Hispanic Asian or Pacific Islanders [APIs]), with a mean age at death of 64.47 ± 13.17 years. During the study period, the ASDR for NAFLD increased by 15% (12.94 to 14.90; AAPC, 1.98%; P < 0.001]), while women (AAPC, 2.99% vs. 1.16% men; P = 0.003), non-Hispanic whites (AAPC, 2.48%), non-Hispanic AIANs (AAPC, 2.31%), and Hispanics (AAPC, 0.74%) experienced the highest annual increases. Stable trends were noted for non-Hispanic blacks and non-Hispanic APIs. Among subgroups, Mexican (AAPC, 1.75%) and Asian Indians (AAPC, 6.94%) experienced annual increases. The top six underlying causes of death (155,894 cirrhosis, 38,444 CVD, 19,466 non-liver cancer, 10,867 HCC, 8,113 DM, and 5,683 lung disease) accounted for 67.5% of NAFLD-related deaths. For cause-specific deaths, ASDR increased for HCC (AAPC, 3.82%), DM (AAPC, 2.23%), non-liver cancer (AAPC, 2.14%), CVD (AAPC, 1.59%), and cirrhosis (AAPC, 0.96%). Conclusion: NAFLD-related deaths in U.S. adults are increasing. Cirrhosis is the top cause-specific death, followed by CVD. Women, non-Hispanic whites, and non-Hispanic AIANs (subgroups Mexicans and Asian Indians) experienced the highest increases in deaths. Policies addressing the societal burden of NAFLD are needed.

Relationships among neurotransmitters, cytokines and cognitive performance for individuals with hepatitis C achieving sustained virologic response: A pilot study.

An important extrahepatic consequence of Hepatitis C is its adverse impact on the central nervous system and cognitive performance. We aimed to determine whether there is a significant relationship between selected neurotransmitters and cytokines and cognitive performance in patients with Chronic Hepatitis C before and after achieving sustained virologic response (SVR). Pre-SVR, elevated kynurenine was associated with increased immediate and delayed visual memory, whereas post-SVR the positive associations are between kynurenine and immediate and delayed verbal memory. TGF-B was consistently negatively associated with both immediate and delayed visual memory pre- and post-SVR. These concomitant changes may have important clinical relevance.

The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: A systematic review and meta-analysis.

BACKGROUND & AIMS: Although non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH) and NASH with advanced fibrosis are closely associated with type 2 diabetes mellitus (T2DM), their global prevalence rates have not been well described. Our aim was to estimate the prevalence of NAFLD, NASH, and advanced fibrosis among patients with T2DM, by regions of the world. METHODS: We searched for terms including NAFLD, NASH and T2DM in studies published from January 1989 to September 2018, using PubMed, Ovid MEDLINE®, EMBASE and Web of Science. Strict exclusion criteria were applied. Regional and global mean prevalence weighted by population size in each country were estimated and pooled using random-effects meta-analysis. Potential sources of heterogeneity were investigated using stratified meta-analysis and meta-regression. RESULTS: Among 80 studies from 20 countries that met our inclusion criteria, there were 49,419 individuals with T2DM (mean age 58.5 years, mean body mass index 27.9 kg/m2, and males 52.9%). The global prevalence of NAFLD among patients with T2DM was 55.5% (95% CI 47.3-63.7). Studies from Europe reported the highest prevalence (68.0% [62.1-73.0%]). Among 10 studies that estimated the prevalence of NASH, the global prevalence of NASH among individuals with T2DM was 37.3% (95% CI 24.7-50.0%). Seven studies estimated the prevalence of advanced fibrosis in patients with NAFLD and T2DM to be 17.0% (95% CI 7.2-34.8). Meta-regression models showed that geographic region and mean age (p <0.5) were associated with the prevalence of NAFLD, jointly accounting for 63.9% of the heterogeneity. CONCLUSIONS: This study provides the global prevalence rates for NAFLD, NASH, and advanced fibrosis in patients with T2DM. These data can be used to estimate the clinical and economic burden of NASH in patients with T2DM around the world. LAY SUMMARY: Non-alcoholic fatty liver disease (NAFLD) is now recognized as the most prevalent chronic liver disease worldwide. Type 2 diabetes mellitus (T2DM) is an important risk factor for NAFLD. Additionally, T2DM seems to accelerate the progression of liver disease in NAFLD. Despite the high prevalence and serious clinical implications of NAFLD in patients with T2DM, it is usually overlooked in clinical practice. This meta-analysis provides evidence of the high prevalence of NAFLD and NASH in patients with T2DM. In this context, increasing awareness about the importance of NAFLD in patients with T2DM among all important stakeholders (primary care physicians, specialists, and health policy makers) must be prioritized.

Cytokine balance is restored as patient-reported outcomes improve in patients recovering from chronic hepatitis C.

BACKGROUND & AIMS: Chronic hepatitis C (CHC) has a negative impact on patient-reported outcomes (PROs). Although most CHC patients who achieve sustained virologic response (SVR) show an improvement in PRO scores, some continue to experience impairment in PROs. The aim was to investigate if serum biomarkers (selected neurotransmitters and cytokines) are associated with changes in PROs in CHC patients who achieve SVR. METHODS: Data were utilized from a prospective clinical trial of ledipasvir/sofosbuvir fixed-dose combination. Chronic genotype 1 HCV subjects without cirrhosis (N = 40, age: 45.3 ± 11.5, 48% male, 90% white) were treated for 12 weeks open label with 97% achieving SVR24. PRO questionnaires included Short Form-36 (SF-36), Fatigue Severity Scale (FSS), Beck Depression Inventory-II (BDI-II), Chronic Liver Disease Questionnaire-HCV (CLDQ-HCV) and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). Sera were used for measurement of selected neurotransmitters and cytokines. Data were collected at baseline and follow-up week 24. RESULTS: Changes in physical health correlated with changes in several biomarkers. BDNF negatively correlated with SF-36 physical health summary score (rho = -0.34, P < 0.05), SF-36 physical functioning (rho = -0.34, P < 0.05), SF-36 bodily pain (rho = -0.39, P < 0.05) and FACIT-F physical well-being (rho = -0.54, P < 0.001). Changes in emotional well-being (FACIT-F) were positively associated with changes in serotonin (rho = 0.34, P < 0.05), but negatively associated with changes in GABA and BDNF (rho = -0.4, P = 0.01, and rho = -0.35, P < 0.05 respectively). CONCLUSIONS: These data indicate relationships between PROs and serum biomarkers pre- and post-SVR in CHC. These concomitant changes may have important clinical relevance.

Impact of hepatitis C virus and insurance coverage on mortality.

OBJECTIVES: To assess the association of payer status and mortality in hepatitis C virus (HCV)-infected patients. STUDY DESIGN: For this retrospective observational study, we used the National Health and Nutrition Examination Survey from 2000 to 2010. Adults with complete data on medical questionnaires, HCV RNA, insurance types, and mortality follow-ups were included. METHODS: We used Cox proportional hazards models to evaluate independent associations of insurance type with mortality in HCV-infected individuals. These models were rerun in the subset of HCV-positive subjects to determine the association of insurance type with mortality. The data used in this study predated the implementation of the Affordable Care Act. RESULTS: Among 19,452 eligible participants, 311 (1.4%) were HCV positive. HCV-positive patients were older, were more likely to be non-Hispanic black and male, and had higher prevalence of hypertension (all P <.001). HCV-positive patients were also less likely to have private insurance and more likely to be covered by Medicaid or be uninsured relative to HCV-negative patients (P <.001). Among HCV-positive patients, after adjustment for confounders, those with Medicaid coverage had an increased risk of mortality compared with those with private insurance (hazard ratio [HR], 6.31; 95% CI, 1.22-29.94) and uninsured individuals (HR, 8.83; 95% CI, 1.56-49.99). CONCLUSIONS: Patients who have HCV are more likely to be uninsured or covered by Medicaid. HCV-positive patients with Medicaid have an increased mortality risk compared with those with private insurance. Given the high burden of HCV infection and adverse prognosis among individuals covered by Medicaid, policy makers must prioritize funding and supporting Medicaid programs.

Cognitive Performance in Individuals With Non-Alcoholic Fatty Liver Disease and/or Type 2 Diabetes Mellitus.

BACKGROUND: Individuals with nonalcoholic fatty liver disease (NAFLD) share some common pathophysiological features with individuals with type 2 diabetes mellitus (T2DM). There is a well-established association between T2DM and cognitive decline, but no corollary data of people with NAFLD and without T2DM or whether combination of the 2 disorders is associated with additive deficits in cognitive performance. OBJECTIVES: The purpose of this investigation is to compare measures of cognitive performance for individuals with NAFLD, individuals with T2DM, individuals with both or neither. METHODS: Using NHANES data from 2011-2014, 1102 individuals were identified who had completed cognitive assessments. RESULTS: After controlling for demographics, comorbidities, and metabolic components, individuals with both NAFLD and T2DM scored significantly lower on a task that combines processing speed, sustained attention, and working memory (Beta = -3.44, 95% CI: -6.75 to -0.12) than individuals with neither. Individuals with T2DM without NAFLD scored significantly lower on verbal fluency (Beta = -1.47, 95% CI: -2.7 to -0.23) than individuals with neither. CONCLUSIONS: Data from this study suggests that individuals with T2DM and individuals with both NAFLD and T2DM have lower cognitive performance on various tasks. These data support an approach that aims to apply preventive strategies to optimize management of T2DM in patients with NAFLD.

Components of metabolic syndrome increase the risk of mortality in nonalcoholic fatty liver disease (NAFLD).

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the United States. Metabolic syndrome (MS) components are highly prevalent in NAFLD. Our aim is to assess the relationship of NAFLD and MS with long-term outcome of mortality.The Third National Health and Nutrition Examination Survey (NHANES) was utilized. NAFLD was diagnosed by ultrasound in the presence of hepatic steatosis and no other causes of chronic liver disease. History of MS and its components were obtained from self-reported NHANES questionnaires. Mortality was obtained from Mortality-Linkage File, through December 31, 2011. Chi-square test was used for categorical variables and Cox proportional models estimated hazard ratios with 95% confidence interval.NAFLD cohort (n = 3613) had a median age of 43 years, 73% white, and 50% male. NAFLD group with at least one MS condition was significantly older, had higher body mass index, more likely to have insulin resistance, and heart disease compared to NAFLD group without MS. Over 19-years of follow-up, 1039 people died. Compared to NAFLD patients without MS, presence of one MS component increased the risk of mortality at 8-year (2.6% vs 4.7%) and 16-year (6% vs 11.9%) (P < .001). After adjusting for socio-demographic factors, NAFLD with all MS components was associated with overall, cardiac and liver-mortality. Increased number of MS components was associated with lower survival (P < .0001).Patients with NAFLD and MS have higher mortality risk compared to NAFLD patients without MS. These NAFLD patients should be prioritized for the development of treatment regimens.