Incidence of liver cancer in young adults according to the global burden of disease database 2019.

OBJECTIVE: The worldwide burden of cancer is increasing in younger populations. However, the epidemiology of primary liver cancer remains understudied in young adults compared to other cancer forms. METHODS: This study analyzed data from the Global Burden of Disease (GBD) study between 2010 and 2019 to assess the age-standardized incidence, mortality, and disability-adjusted life years (DALYs) associated with primary liver cancer in the young (15-49 y), stratified by region, nation, sociodemographic index, and sex. RESULTS: The study found a global estimate of 78,299 primary liver cancer cases, 60,602 deaths, and 2.90 million DALYs in the young population. The Western Pacific region exhibited the highest burden in 2019, showing the most significant increase compared to other regions between 2010-2019. More than half of countries worldwide have undergone an increase in primary liver cancer incidence rates in young adults. Around 12.51% of deaths due to primary liver cancer occur in young individuals. Throughout the study period, there was a significant decline in primary liver cancer mortality due to most etiologies, except for metabolic dysfunction-associated steatotic liver disease (MASLD)-attributable primary liver cancer (annual percentage change [APC] +0.87%, 95% confidence interval 0.70-1.05%) and alcohol-attributable primary liver cancer (APC +0.21%, 95% confidence interval 0.01-0.42%). Limitations of the GBD database include reliance on the quality of primary data and possible underestimation of alcohol consumption. CONCLUSION: Over the past decade, there has been a marked increase in the burden of primary liver cancer, especially that originating from steatotic liver disease. This trend calls for the development of urgent and comprehensive strategies to mitigate this rising burden globally.

Alcohol-related liver disease: A global perspective.

Alcohol-associated liver disease (ALD) represents one of the deadliest yet preventable consequences of excessive alcohol use. It represents 5.1 % of the global burden of disease, mainly involving the productive-age population (15-44 years) and leading to an increased mortality risk from traffic road injuries, suicide, violence, cardiovascular disease, neoplasms, and liver disease, among others, accounting for 5.3 % of global deaths. Daily alcohol consumption, binge drinking (BD), and heavy episodic drinking (HED) are the patterns associated with a higher risk of developing ALD. The escalating global burden of ALD, even exceeding what was predicted, is the result of a complex interaction between the lack of public policies that regulate alcohol consumption, low awareness of the scope of the disease, late referral to specialists, underuse of available medications, insufficient funds allocated to ALD research, and non-predictable events such as the COVID-19 pandemic, where increases of up to 477 % in online alcohol sales were registered in the United States. Early diagnosis, referral, and treatment are pivotal to achieving the therapeutic goal in patients with alcohol use disorder (AUD) and ALD, where complete alcohol abstinence and prevention of alcohol relapse are expected to enhance overall survival. This can be achieved through a combination of cognitive behavioral, motivational enhancement and pharmacological therapy. Furthermore, the appropriate use of available pharmacological therapy and implementation of public policies that comprehensively address this disease will make a real difference.

Global and regional burden of alcohol-associated liver disease and alcohol use disorder in the elderly.

Background & Aims: Alcohol-associated liver diseases (ALDs) and alcohol use disorder (AUD) pose a global health risk. AUD is underrecognized in the elderly, and the burden of AUD complications, including ALD, may increase with aging populations and rising alcohol intake. However, there is a lack of epidemiological evidence on AUD and ALD in the elderly. Methods: Using the Global Burden of Disease Study 2019, we analyzed the prevalence, mortality, disability-adjusted life years (DALYs), age-standardized rates (ASRs), and temporal change from 2000 to 2019 of ALD and AUD in the overall population and the elderly (65-89 years). The findings were categorized by sex, region, nation, and sociodemographic index. Results: The prevalence rates of ALD in the elderly were higher than those in adolescents and young adults, whereas AUD levels were lower than those in adolescents and young adults. In 2019, there were 9.39 million cases (8.69% of cases in the overall population) of AUD, 3.23 million cases (21.8% of cases in the overall population) of alcohol-associated cirrhosis, and 68,468 cases (51.27% of cases in the overall population) of liver cancer from alcohol among the elderly. ASRs of the prevalence of ALD and AUD in the elderly increased in most regions; on the contrary, ASRs of death and DALYs decreased in most regions. Nevertheless, ASRs of death and DALYs from liver cancer from alcohol increased in many areas. Conclusions: Our findings highlighted the increased prevalence of ALD in the elderly, with a burden of AUD comparable with that in the overall population. Public health strategies on ALD and AUD targeting the elderly are urgently needed. Impact and implications: The burden of alcohol-associated liver disease (ALD) and alcohol use disorder (AUD) is increasing. Advances in healthcare and education have resulted in a remarkable spike in life expectancy and a consequential population aging. Nevertheless, little is known about the epidemiology of ALD and AUD in the elderly. Our study indicates the increasing burden of ALD and AUD in the elderly population, necessitating early detection, intervention, and tailored care to the unique needs and complexities faced by older individuals grappling with these conditions.

Review article: Current indications and selection criteria for early liver transplantation in severe alcohol-associated hepatitis.

BACKGROUND: Alcohol-associated hepatitis (AH) is a severe inflammatory form of alcohol-associated liver disease (ALD) that carries a high mortality rate. Early liver transplantation for severe AH is increasingly available. However, specific criteria for referral and selection remain a subject of debate. AIMS: To provide a narrative review of the natural history, diagnostic criteria and indications for referral for early liver transplantation for severe AH. METHODS: We searched PubMed for articles published through August 2023. Key search terms were 'alcoholic hepatitis,' 'alcohol-associated hepatitis,' 'abstinence,' 'alcohol relapse,' and 'liver transplantation.' RESULTS: Previously, a six-month period of alcohol abstinence was required before patients with ALD were considered for liver transplantation. However, studies in recent years have demonstrated that, among carefully selected patients, patients who received early transplants have much higher survival rates than patients with similarly severe disease who did not undergo transplants (77% vs. 23%). Despite these successes, early liver transplantation remains controversial, as these patients have typically not undergone treatment for alcohol use disorder, with the ensuing risk of returning to alcohol use. CONCLUSIONS: While early liver transplantation for AH has survival benefits, many patients would not have received treatment for alcohol use disorder. An integrated approach to evaluating candidacy for early liver transplantation is needed.

Racial and ethnic disparities in alcohol-associated liver disease in the United States: A systematic review and meta-analysis.

BACKGROUND: Alcohol-associated liver disease (ALD), encompassing alcohol-associated hepatitis and alcohol-associated cirrhosis, is rising in the United States. Racial and ethnic disparities are evident within ALD; however, the precise nature of these disparities is poorly defined. METHODS: We conducted a search of the PubMed/MEDLINE and EMBASE databases to identify studies published from inception through September 2023 that reported ALD incidence, prevalence, and mortality within the United States, stratified by race and ethnicity. We calculated pooled prevalence and incidence by race and ethnicity, including risk ratios and ORs for ALD pooled prevalence and alcohol-associated hepatitis/alcohol-associated cirrhosis pooled proportions, and OR for ALD mortality using the DerSimonian and Laird method for random-effect models. RESULTS: We identified 25 relevant studies (16 for quantitative meta-analysis), comprising 76,867,544 patients. ALD prevalence was highest in Hispanic (4.5%), followed by White (3.1%) and Black (1.4%) individuals. Pooled risk ratios of ALD prevalence were 1.64 (95% CI: 1.12-2.39) for Hispanic and 0.59 (95% CI: 0.35-0.87) for Black compared to White individuals. Mortality among those with ALD did not significantly differ between White and Hispanic (OR: 1.54, 95% CI: 0.9-2.5; I2=0%), Black (OR: 1.2, 95% CI: 0.8-1.6; I2=0%), or Native American (OR: 2.41, 95% CI: 0.9-2.9) individuals, while there was a significant difference between White and Asian (OR: 0.1; 95% CI: 0.03-0.5) individuals. Most data were cross-sectional and assessed to be of poor or fair quality. CONCLUSIONS: Differences were observed in ALD epidemiology, including higher prevalence among Hispanic and lower prevalence among Black individuals, although there were smaller differences in ALD mortality. Differences in ALD prevalence and prognosis remain poorly defined based on existing data, highlighting a need for higher-quality epidemiological studies in this area.

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

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

Racial and Ethnic Disparities in Liver Transplantation for Alcohol-associated Liver Diseases in the United States.

BACKGROUND: Emerging data suggest disparities exist in liver transplantation (LT) for alcohol-associated liver disease (ALD). As the incidence of ALD increases, we aimed to characterize recent trends in ALD LT frequency and outcomes, including racial and ethnic disparities. METHODS: Using United Network for Organ Sharing/Organ Procurement and Transplantation Network data (2015 through 2021), we evaluated LT frequency, waitlist mortality, and graft survival among US adults with ALD (alcohol-associated hepatitis [AH] and alcohol-associated cirrhosis [AAC]) stratified by race and ethnicity. We used adjusted competing-risk regression analysis to evaluate waitlist outcomes, Kaplan-Meier analysis to illustrate graft survival, and Cox proportional hazards modeling to identify factors associated with graft survival. RESULTS: There were 1211 AH and 26 526 AAC new LT waitlist additions, with 970 AH and 15 522 AAC LTs performed. Compared with non-Hispanic White patients (NHWs) with AAC, higher hazards of waitlist death were observed for Hispanic (subdistribution hazard ratio [SHR] = 1.23, 95% confidence interval [CI]: 1.16-1.32), Asian (SHR = 1.22, 95% CI:1. 01-1.47), and American Indian/Alaskan Native (SHR = 1.42, 95% CI: 1.15-1.76) candidates. Similarly, significantly higher graft failures were observed in non-Hispanic Black (HR = 1.32, 95% CI: 1.09-1.61) and American Indian/Alaskan Native (HR = 1.65, 95% CI: 1.15-2.38) patients with AAC than NHWs. We did not observe differences in waitlist or post-LT outcomes by race or ethnicity in AH, although analyses were limited by small subgroups. CONCLUSIONS: Significant racial and ethnic disparities exist for ALD LT frequency and outcomes in the United States. Compared with NHWs, racial and ethnic minorities with AAC experience increased risk of waitlist mortality and graft failure. Efforts are needed to identify determinants for LT disparities in ALD that can inform intervention strategies.

The burden of liver disease in Latin America.

Liver disease poses a substantial burden in Latin America. This burden is primarily attributed to a high level of alcohol consumption and the increasing prevalence of risk factors associated with metabolic dysfunction-associated steatotic liver disease (MASLD), such as sedentary lifestyles, easy access to ultra-processed foods, obesity, and type 2 diabetes mellitus. These epidemiological trends are cause for concern, especially considering that there are significant challenges in addressing them, due to disparities in access to liver disease screening and care. In this article, we aim to provide an overview of the current situation regarding liver disease in Latin America. We also discuss recent multinational proposals designed to address the growing MASLD burden via its integration into existing non-communicable diseases policies, at both local and global levels. Additionally, we emphasize the urgent need to establish effective public health policies that target both MASLD risk factors and excessive alcohol consumption. Furthermore, we discuss the development of liver transplantation programs, areas for improvement in medical education and research capabilities, and how the fostering of extensive collaboration among all stakeholders is crucial for addressing liver disease in the region.

New insights into the molecular basis of alcohol abstinence and relapse in alcohol-associated liver disease.

Alcohol use disorder remains a significant public health concern, affecting around 5% of adults worldwide. Novel pathways of damage have been described during the last years, providing insight into the mechanism of injury due to alcohol misuse beyond the direct effect of ethanol byproducts on the liver parenchyma and neurobehavioral mechanisms. Thus, the gut-liver-brain axis and immune system involvement could be therapeutic targets for alcohol use disorder. In particular, changes in gut microbiota composition and function, and bile acid homeostasis, have been shown with alcohol consumption and cessation. Alcohol can also directly disrupt intestinal and blood-brain barriers. Activation of the immune system can be triggered by intestinal barrier dysfunction and translocation of bacteria, pathogen-associated molecular patterns (such as lipopolysaccharide), cytokines, and damage-associated molecular patterns. These factors, in turn, promote liver and brain inflammation and the progression of liver fibrosis. Other involved mechanisms include oxidative stress, apoptosis, autophagy, and the release of extracellular vesicles and miRNA from hepatocytes. Potential therapeutic targets include gut microbiota (probiotics and fecal microbiota transplantation), neuroinflammatory pathways, as well as neuroendocrine pathways, for example, the ghrelin system (ghrelin receptor blockade), incretin mimetics (glucagon-like peptide-1 analogs), and the mineralocorticoid receptor system (spironolactone). In addition, support with psychological and behavioral treatments is essential to address the multiple dimensions of alcohol use disorder. In the future, a personalized approach considering these novel targets can contribute to significantly decreasing the alcohol-associated burden of disease.

Active alcohol consumption is associated with acute-on-chronic liver failure in Hispanic patients.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is a severe clinical entity associated with elevated short-term mortality. We aimed to characterize patients with decompensated cirrhosis according to presence of ACLF, their association with active alcohol intake, and long-term survival in Latin America. METHODS: Retrospective cohort study of decompensated cirrhotic in three Chilean university centers (2017-2019). ACLF was diagnosed according EASL-CLIF criteria. We assessed survival using competing-risk and time-to-event analyses. We evaluated the time to death using accelerated failure time (AFT) models. RESULTS: We included 320 patients, median age of 65.3±11.7 years old, and 48.4% were women. 92 (28.7%) patients met ACLF criteria (ACLF-1: 29.3%, ACLF-2: 27.1%, and ACLF-3: 43.4%). The most common precipitants were infections (39.1%), and the leading organ failure was kidney (59.8%). Active alcohol consumption was frequent (27.7%), even in patients with a prior diagnosis of non-alcoholic fatty liver disease (NAFLD) (16.2%). Ninety-two (28.7%) patients had ACLF (ACLF-1: 8.4%, ACLF-2: 7.8%, and ACLF-3: 12.5%). ACLF patients had a higher MELD-Na score at admission (27 [22-31] versus 16 [12-21], p<0.0001), a higher frequency of alcohol-associated liver disease (36.7% versus 24.9%, p=0.039), and a more frequent active alcohol intake (37.2% versus 23.8%, p=0.019). In a multivariate model, ACLF was associated with higher mortality (subdistribution hazard ratio 1.735, 95%CI: 1.153-2.609; p<0.008). In the AFT models, the presence of ACLF during hospitalization correlated with a shorter time to death: ACLF-1 shortens the time to death by 4.7 times (time ratio [TR] 0.214, 95%CI: 0.075-0.615; p<0.004), ACLF-2 by 4.4 times (TR 0.224, 95%CI: 0.070-0.713; p<0.011), and ACLF-3 by 37 times (TR 0.027, 95%CI: 0.006-0.129; p<0.001). CONCLUSIONS: Patients with decompensated cirrhosis and ACLF exhibited a high frequency ofactive alcohol consumption. Patients with ACLF showed higher mortality and shorter time todeath than those without ACLF.

The intersection between alcohol-related liver disease and nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD) are the leading causes of chronic liver disease worldwide. NAFLD and ALD share pathophysiological, histological and genetic features and both alcohol and metabolic dysfunction coexist as aetiological factors in many patients with hepatic steatosis. A diagnosis of NAFLD requires the exclusion of significant alcohol consumption and other causes of liver disease. However, data suggest that significant alcohol consumption is often under-reported in patients classified as having NAFLD and that alcohol and metabolic factors interact to exacerbate the progression of liver disease. In this Review, we analyse existing data on the interaction between alcohol consumption and metabolic syndrome as well as the overlapping features and differences in the pathogenesis of ALD and NAFLD. We also discuss the clinical implications of the coexistence of alcohol consumption, of any degree, in patients with evidence of metabolic derangement as well as the use of alcohol biomarkers to detect alcohol intake. Finally, we summarize the evolving nomenclature of fatty liver disease and describe a recent proposal to classify patients at the intersection of NAFLD and ALD. We propose that, regardless of the presumed aetiology, patients with fatty liver disease should be evaluated for both metabolic syndrome and alcohol consumption to enable better prognostication and a personalized medicine approach.

Development and validation of nonalcoholic fatty liver disease test: a simple sensitive and specific marker for early diagnosis of nonalcoholic fatty liver disease.

AIM: This study aimed to develop a noninvasive test for identifying patients with nonalcoholic fatty liver disease (NAFLD) based on clinical and routine laboratory data. METHODS: The developed model 'NAFLD test' was compared to the most commonly used NAFLD scores and then validated in three groups of NAFLD patients from five centers in Egypt, China, and Chile. Patients were divided into the discovery cohort (n = 212) and the validation study (n = 859). The ROC curve and stepwise multivariate discriminant analysis were used to develop and validate the NAFLD test and evaluate its diagnostic performance, which was then compared to other NAFLD scores. RESULTS: Elevated C-reactive protein (CRP), cholesterol, BMI, and alanine aminotransferase (ALT) levels were significantly associated with NAFLD (P < 0.0001). NAFLD test is depicted as (-0.695 + 0.031 × BMI + 0.003 × cholesterol + 0.014 × ALT + 0.025 × CRP) to discriminate patients with NAFLD from healthy individuals. The area under the ROC curve (AUC) of the NAFLD test was 0.92 [95% confidence interval (CI): 0.88-0.96]. The NAFLD test was the most accurate diagnostic indicator of NAFLD when compared to widely used NAFLD indices. Upon validating the NAFLD test, its AUC (95% CI) for distinguishing patients with NAFLD from healthy individuals was 0.95 (0.94-0.97), 0.90 (0.87-0.93), and 0.94 (0.91-0.97) in Egyptian, Chinese, and Chilean patients with NAFLD respectively. CONCLUSION: The NAFLD test is a new validated diagnostic biomarker that can be utilized for the early diagnosis of NAFLD with high diagnostic performance.

MELD 3.0 adequately predicts mortality and renal replacement therapy requirements in patients with alcohol-associated hepatitis.

Background & Aims: Model for End-Stage Liver Disease (MELD) score better predicts mortality in alcohol-associated hepatitis (AH) but could underestimate severity in women and malnourished patients. Using a global cohort, we assessed the ability of the MELD 3.0 score to predict short-term mortality in AH. Methods: This was a retrospective cohort study of patients admitted to hospital with AH from 2009 to 2019. The main outcome was all-cause 30-day mortality. We compared the AUC using DeLong's method and also performed a time-dependent AUC with competing risks analysis. Results: A total of 2,124 patients were included from 28 centres from 10 countries on three continents (median age 47.2 ± 11.2 years, 29.9% women, 71.3% with underlying cirrhosis). The median MELD 3.0 score at admission was 25 (20-33), with an estimated survival of 73.7% at 30 days. The MELD 3.0 score had a better performance in predicting 30-day mortality (AUC:0.761, 95%CI:0.732-0.791) compared with MELD sodium (MELD-Na; AUC: 0.744, 95% CI: 0.713-0.775; p = 0.042) and Maddrey's discriminant function (mDF) (AUC: 0.724, 95% CI: 0.691-0.757; p = 0.013). However, MELD 3.0 did not perform better than traditional MELD (AUC: 0.753, 95% CI: 0.723-0.783; p = 0.300) and Age-Bilirubin-International Normalised Ratio-Creatinine (ABIC) (AUC:0.757, 95% CI: 0.727-0.788; p = 0.765). These results were consistent in competing-risk analysis, where MELD 3.0 (AUC: 0.757, 95% CI: 0.724-0.790) predicted better 30-day mortality compared with MELD-Na (AUC: 0.739, 95% CI: 0.708-0.770; p = 0.028) and mDF (AUC:0.717, 95% CI: 0.687-0.748; p = 0.042). The MELD 3.0 score was significantly better in predicting renal replacement therapy requirements during admission compared with the other scores (AUC: 0.844, 95% CI: 0.805-0.883). Conclusions: MELD 3.0 demonstrated better performance compared with MELD-Na and mDF in predicting 30-day and 90-day mortality, and was the best predictor of renal replacement therapy requirements during admission for AH. However, further prospective studies are needed to validate its extensive use in AH. Impact and implications: Severe AH has high short-term mortality. The establishment of treatments and liver transplantation depends on mortality prediction. We evaluated the performance of the new MELD 3.0 score to predict short-term mortality in AH in a large global cohort. MELD 3.0 performed better in predicting 30- and 90-day mortality compared with MELD-Na and mDF, but was similar to MELD and ABIC scores. MELD 3.0 was the best predictor of renal replacement therapy requirements. Thus, further prospective studies are needed to support the wide use of MELD 3.0 in AH.

Inpatient Hepatology Consultation: A Practical Approach for Clinicians.

Cirrhosis is the end-stage of chronic liver disease and constitutes a leading cause of potential years of working life lost, especially in the Americas and Europe. Its natural history is characterized by an asymptomatic phase called compensated cirrhosis, followed by a rapidly progressive phase characterized by liver-related complications termed decompensated cirrhosis. Complications could be related to portal hypertension and/or liver dysfunction, including ascites, portal hypertensive gastrointestinal bleeding, encephalopathy, and jaundice. This review will discuss some of the most important precipitants of hepatic decompensation, including acute variceal bleeding, spontaneous bacterial peritonitis, and hepatic encephalopathy.

High prevalence of SARS-CoV-2 detection and prolonged viral shedding in stools: A systematic review and cohort study / Elevada detección de SARS-CoV-2 y prolongada excreción viral en deposiciones: Estudio de cohorte y revisión sistemática

Objectives: To: 1. Describe the frequency of viral RNA detection in stools in a cohort of patients infected with SARS-CoV-2, and 2. Perform a systematic review to assess the clearance time in stools of SARS-CoV-2. Methods: We conducted a prospective cohort study in two centers between March and May 2020. We included SARS-CoV-2 infected patients of any age and severity. We collected seriated nasopharyngeal swabs and stool samples to detect SARS-CoV-2. After, we performed a systematic review of the prevalence and clearance of SARS-CoV-2 in stools (PROSPERO-ID: CRD42020192490). We estimated prevalence using a random-effects model. We assessed clearance time by using Kaplan–Meier curves. Results: We included 32 patients; mean age was 43.7±17.7 years, 43.8% were female, and 40.6% reported gastrointestinal symptoms. Twenty-five percent (8/32) of patients had detectable viral RNA in stools. The median clearance time in stools of the cohort was 11[10–15] days. Systematic review included 30 studies (1392 patients) with stool samples. Six studies were performed in children and 55% were male. The pooled prevalence of viral detection in stools was 34.6% (twenty-four studies, 1393 patients; 95%CI:25.4–45.1); heterogeneity was high (I2:91.2%, Q:208.6; p≤0.001). A meta-regression demonstrates an association between female-gender and lower presence in stools (p=0.004). The median clearance time in stools was 22 days (nineteen studies, 140 patients; 95%CI:19–25). After 34 days, 19.9% (95%CI:11.3–29.7) of patients have a persistent detection in stools. Conclusions: Detection of SARS-CoV-2 in stools is a frequent finding. The clearance of SARS-CoV-2 in stools is prolonged and it takes longer than nasopharyngeal secretions.(AU)

Objetivos: 1. Evaluar la detección de ARN viral en deposiciones y su tiempo de excreción en una cohorte de pacientes con SARS-CoV-2; 2. Realizar una revisión sistemática para evaluar el tiempo de excreción en deposiciones del SARS-CoV-2. Métodos: Estudio de cohorte prospectiva en dos centros entre marzo-mayo del 2020. Incluimos pacientes infectados con SARS-CoV-2 de cualquier edad y gravedad. Recolectamos secreciones nasofaríngeas y deposiciones en forma seriada para detectar SARS-CoV-2. También realizamos una revisión sistemática de la prevalencia y excreción del SARS-CoV-2 en deposiciones (PROSPERO-ID: CRD42020192490). Estimamos la prevalencia usando un modelo de efectos aleatorios. Evaluamos el tiempo de excreción usando curvas Kaplan-Meier. Resultados: Incluimos 32 pacientes; edad media 43 ± 17,7 años, 43,8% eran mujeres y 40,6% reportaron síntomas gastrointestinales. Veinticinco por ciento (8/32) tenían ARN viral detectable en deposiciones. La mediana de excreción en deposiciones fue 11 [10-15] días. La revisión sistemática incluyó 30 estudios (1.392 pacientes) con muestras en deposiciones. Seis estudios fueron realizados en niños y 55% eran hombres. La prevalencia estimada de detección viral en deposiciones fue de 34,6% (24 estudios, 1.393 pacientes; IC 95%: 25,4-45,1); la heterogeneidad fue elevada (I2: 91,2%; Q: 208,6; p ≤ 0,001). Una metarregresión demostró una asociación entre el género femenino y menor prevalencia en deposiciones (p = 0,004). La mediana de tiempo de excreción fueron 22 días (19 estudios, 140 pacientes; IC 95%: 19-25). Tras 34 días, 19,9% (IC 95%: 11,3-29,7) de los pacientes tenían detección persistente en deposiciones. Conclusiones: La detección de SARS-CoV-2 en deposiciones es un hallazgo frecuente. La excreción del SARS-CoV-2 en deposiciones es prolongada y es más tardía que en secreciones nasofaríngeas.(AU)

Phantosmia May Predict Long-Term Measurable Olfactory Dysfunction After COVID-19.

OBJECTIVES: Persistent olfactory dysfunction (OD) after 6 months caused by SARS-CoV-2 infection has been reported with a variable prevalence worldwide. This study aimed to determine the prevalence of long-term OD and identify predisposing factors. METHODS: A prospective cohort study was conducted on 100 adults with COVID-19. Olfactory function was assessed with the University of Pennsylvania Smell Identification Test and a symptom survey at the onset of disease and 30 days later. Patients with persistent quantitative OD at the second assessment were reevaluated after 1 year. Demographic variables, symptoms, and the degree of smell loss were analyzed. RESULTS: Participants included 100 patients. The mean age was 42.2 ± 15.6 years, 55 (55%) were female, and 56 (56%) were outpatients. Baseline smell loss was identified in 75/100 (75%) patients, decreasing to 39/95 (40%) after 1 month, and persisting in 29 patients after 1 year. Phantosmia at baseline was the only risk factor identified for persistent OD after 1 year (relative risk 2.51; 95% confidence interval 1.53-4.12; p < 0.001). Regardless of the outcome in smell function, a significant decline in olfaction was associated with the presence of phantosmia at 1 month (ß = -12.39; 95% CI -19.82 to -4.95; p < 0.01). CONCLUSIONS: SARS-CoV-2 (2019-2020 variants) produced a highly frequent OD that persisted in 29% of the patients after 1 year. The presence of phantosmia at baseline and 1 month was associated with a worse evolution, but phantosmia may interfere with the performance in an identification smell test. A longer follow-up is required in these patients. LEVEL OF EVIDENCE: 2 Laryngoscope, 132:2445-2452, 2022.