Pathways to Poor Adherence to Antiretroviral Therapy Among People Living with HIV: The Role of Food Insecurity and Alcohol Misuse.

Daily adherence to antiretroviral therapy (ART) increases the length and quality of life of people living with HIV (PLHIV). We explored whether socioeconomic status directly impacts ART adherence and whether part of the effect is mediated by pathways through alcohol misuse or food insecurity. A cross-sectional study was conducted in Rio de Janeiro/Brazil (November/2019 to March/2020) with PLHIV aged ≥ 18 years. Validated instruments were used to measure alcohol use, food insecurity, and ART adherence. Using structural equation modeling we assessed the direct and indirect effects of variables on ART adherence. Participants reported significant challenges: hunger: 12%, alcohol use: 64%, and missing ART doses: 24%. Results showed that lower socioeconomic status increased poor adherence and that this effect was mediated through higher food insecurity. Alcohol misuse also increased poor adherence through a strong direct effect. Providing socio-economic support coupled with interventions to mitigate alcohol's harmful impact can aid HIV care.

RESUMEN: La adherencia diaria a la terapia antirretroviral (TAR) aumenta la duración y calidad de vida de las personas que viven con el VIH (PVVIH). Exploramos si el estatus socioeconómico afecta directamente la adherencia al TAR y si parte del efecto está mediado por vías a través del abuso del alcohol o la inseguridad alimentaria. Se realizó un estudio en Río de Janeiro/Brasil (noviembre/2019 a marzo/2020) con PVVIH con edad ≥ 18 años. Utilizando modelos de ecuaciones estructurales evaluamos los efectos directos e indirectos. Los participantes informaron desafíos significativos: hambre: 12%, consumo de alcohol: 64%, mala adherencia: 24%. Los resultados mostraron que un nivel socioeconómico más bajo aumentaba la mala adherencia por un efecto mediado por mayor inseguridad alimentaria. Abuso de alcohol también aumentó la mala adherencia por un fuerte efecto directo. Brindar apoyo socioeconómico con intervenciones para mitigar el impacto nocivo del alcohol puede ayudar la atención clínica.

Acceptability and usability of oral fluid HCV self-testing for hepatitis C diagnosis: A systematic review and meta-analysis.

Data on the acceptability and usability of hepatitis C virus self-testing (HCVST) remain scarce. We estimated the pooled rates of acceptability/feasibility and re-reading/re-testing agreement of HCVST using oral fluid tests (PROSPERO-CRD42022349874). We searched online databases for studies that evaluated acceptability, usability and inter-reader/operator variability for HCVST using oral fluid tests. Pooled estimates of feasibility, agreement and post-testing perspectives were analysed. Sensitivity analyses were performed in men who have sex with men (MSM) and people who inject drugs (PWID). Heterogeneity was assessed using the I2 statistics. A total of six studies comprising 870 participants were identified: USA (n = 95 with liver disease), Kenya (n = 150 PWID), Egypt (n = 116 from the general population), Vietnam (n = 104 MSM and n = 105 PWID), China (n = 100 MSM) and Georgia (n = 100 MSM and n = 100 PWID)]. All studies used OraQuick® HCV Rapid Antibody Test. The pooled overall estimates for correct sample collection and for people who performed HCVST without needing assistance in any step (95% confidence interval [CI]) were 87.2% [76.0-95.3] (n = 755; I2 = 93.7%) and 62.6% [37.2-84.8] (n = 755; I2 = 98.0%), respectively. The pooled estimate of agreement for re-reading was 95.0% [95% CI 91.5-97.6] (n = 831; I2 = 74.0%) and for re-testing was 94.4% [90.3-97.5] (n = 726; I2 = 77.1%). The pooled estimate of those who would recommend HCVST was 94.4% [84.7-99.6] (n = 625; I2 = 93.7%). Pooled estimates (95% CI) of correct sample collection (72.8% [63.3-81.5] vs. 90.8% [85.9-94.8]) and performance of HCVST without needing assistance (44.1% [14.1-76.7] vs. 78.1% [53.4-95.3]) was lower in PWID compared to MSM. In summary, HCV testing with oral fluid HCVST was feasible and well-accepted. Oral fluid HCVST should be considered in key populations for uptake HCV testing.

Immunogenicity and Safety of Hepatitis B Virus (HBV) Vaccine With a Toll-Like Receptor 9 Agonist Adjuvant in HBV Vaccine-Naïve People With Human Immunodeficiency Virus.

In this international, multicenter open-label study (ACTG A5379) of HepB-CpG vaccine in people with human immunodeficiency virus (HIV) without prior hepatitis B virus (HBV) vaccination, all 68 participants achieved HBV seroprotective titers after the 3-dose series in the primary analysis. No unexpected safety issues were observed.

Validation of the Baveno VI criteria to rule out high-risk varices using hepatic shear-wave elastography.

INTRODUCTION AND OBJECTIVES: Liver stiffness measurement (LSM) by transient elastography has been validated to predict high-risk varices (HRV). We aimed to evaluate the accuracy of shear-wave elastography (SWE) and platelet count (Baveno VI criteria) to rule out HRV in patients with compensated advanced chronic liver disease (c-ACLD). METHODS: This retrospective study analyzed data of patients with c-ACLD (transient elastography ≥ 10 kPa) submitted to two-dimensional SWE (2D-SWE) (GE-LOGIQ-S8) and/or point SWE (p-SWE) (ElastPQ) who had a gastrointestinal endoscopy within 24 months. HRV definition was a large size and presence of red wale marks or sequelae from previous treatment. Optimal thresholds of SWE systems for HRV were identified. The proportion of spared gastrointestinal endoscopies and missing HRV considering a favorable SWE Baveno VI criteria were assessed. RESULTS: Eighty patients [36% male, median age = 63 (interquartile range, 57-69) years] were included. The prevalence of HRV was 34% ( n  = 27/80). The optimal thresholds to predict HRV were 10 kPa and 12 kPa for 2D-SWE and p-SWE, respectively. A favorable 2D-SWE Baveno VI criteria (LSM < 10 kPa and platelets count > 150 × 10 9 /mm 3 ) avoided 19% of gastrointestinal endoscopies without missing HRVs. A favorable p-SWE Baveno VI criteria (LSM < 12 kPa and platelets count > 150 × 10 9 /mm 3 ) spared 20% of gastrointestinal endoscopy without missing HRVs. Using a lower threshold of platelet count (<110 × 10 9 /mm 3 , expanded Baveno VI), 2D-SWE (<10 kPa) avoided 33% of gastrointestinal endoscopy with 8% of missing HRVs, while p-SWE (<12 kPa) avoided 36% of gastrointestinal endoscopy with 5% of missing HRVs. CONCLUSION: LSM by p-SWE or 2D-SWE combined with platelet count (Baveno VI criteria) can spare a considerable number of gastrointestinal endoscopies missing a negligible proportion of HRV.

Accuracy and concordance of two-dimensional shear-wave elastography using transient elastography as the reference in chronic viral hepatitis and HIV infection in Rio de Janeiro, Brazil.

OBJECTIVES: Evaluate the accuracy and agreement of two-dimensional shear-wave elastography (2D-SWE) LOGIQ-S8 with transient elastography in patients from Rio de Janeiro, Brazil. METHOD: This retrospective study compared liver stiffness measurements (LSMs) using transient elastography (M and XL probes) and 2D-SWE GE-LOGIQ-S8 performed by a single experienced operator on the same day in 348 consecutive individuals with viral hepatitis or HIV infection. Suggestive and highly suggestive compensated-advanced chronic liver disease (c-ACLD) were defined by transient elastography-LSM ≥10 kPa and ≥15 kPa, respectively. Agreement between techniques and accuracy of 2D-SWE using transient elastography-M probe as the reference was assessed. Optimal cut-offs for 2D-SWE were identified using the maximal Youden index. RESULTS: Three hundred five patients [61.3% male, median age = 51 [interquartile range (IQR), 42-62] years, 24% with hepatitis C virus (HCV) ± HIV; 17% with hepatitis B virus (HBV) ± HIV; 31% were HIV mono-infected and 28% had HCV ± HIV post-sustained virological response] were included. The overall correlation (Spearman's ρ ) was moderate between 2D-SWE and transient elastography-M ( ρ = 0.639) and weak between 2D-SWE and transient elastography-XL ( ρ = 0.566). Agreements were strong ( ρ > 0.800) in people with HCV or HBV mono-infection, and poor in HIV mono-infected ( ρ > 0.400). Accuracy of 2D-SWE for transient elastography-M ≥ 10 kPa [area under the receiver operating characteristic (AUROC) = 0.91 (95% confidence interval [CI], 0.86-0.96); optimal cut-off = 6.4 kPa, sensitivity = 84% (95% CI, 72-92), specificity = 89% (95% CI, 84-92)] and for transient elastography-M ≥ 15 kPa [AUROC = 0.93 (95% CI, 0.88-0.98); optimal cut-off = 7.1 kPa; sensitivity = 91% (95% CI, 75-98), specificity = 89% (95% CI, 85-93)] were excellent. CONCLUSION: 2D-SWE LOGIQ-S8 system had a good agreement with transient elastography and an excellent accuracy to identify individuals at high risk for c-ACLD.

Inflammasome genes polymorphisms are associated with progression to mechanical ventilation and death in a cohort of hospitalized COVID-19 patients in a reference hospital in Rio de Janeiro, Brazil.

COVID-19 has a broad spectrum of clinical manifestations. We assessed the impact of single nucleotide polymorphisms (SNPs) of inflammasome genesas risk factors for progression toCOVID-19 critical outcomes, such as mechanical ventilation support (MVS) or death.The study included 451 hospitalized individuals followed up at the INI/FIOCRUZ, Rio de Janeiro, Brazil, from 06/2020 to 03/2021. SNPs genotyping was determined by Real-Time PCR. We analyzed risk factors for progression to MVS (n = 174[38.6 %]) or death (n = 175[38.8 %])as a result of COVID-19 by Cox proportional hazardmodels.Slower progression toMVSwas associated with allele G (aHR = 0.66;P = 0.005) or the genotype G/G (aHR = 0.391;P = 0.006) in the NLRP3 rs10754558 or the allele G (aHR = 0.309;P = 0.004) in the IL1ßrs1143634, while C allele in the NLRP3 rs4612666 (aHR = 2.342;P = 0.006) or in the rs10754558 (aHR = 2.957;P = 0.005) were associated with faster progression to death. Slower progression to death was associated to allele G (aHR = 0.563;P = 0.006) or the genotype A/G (aHR = 0.537;P = 0.005) in the CARD8 rs6509365; the genotype A/C in the IFI16 rs1101996 (aHR = 0.569;P = 0.011); the genotype T/T (aHR = 0.394;P = 0.004) or allele T (aHR = 0.68;P = 0.006) in the NLRP3 rs4612666, and the genotype G/G (aHR = 0.326;P = 0.005) or allele G (aHR = 0,68;P = 0.014) in the NLRP3 rs10754558. Our results suggest that inflammasome genetic variations might influence the critical clinical course of COVID-19.

Hepatitis of unknown etiology in children in Brazil: A new challenge or the usual scenario ?

BACKGROUND: An outbreak of acute hepatitis of unknown etiology in children was recently reported worldwide. We aimed to describe the burden of hospitalizations due to hepatitis of unknown etiology in children/adolescents in Brazilian public hospitals. METHODS: We retrieved a database of all hospitalizations in the Brazilian Unified Health System (SUS) from January/2019 to February/2022 using the "microdatasus" R package. Hepatitis of unknown etiology was defined by the following International Classification of Diseases [ICD-10] codes: B19, B19.0, B19.9, K72.0, K72.9, K75, K75.9, R94.5, or R93.2. The incidence rates (95% confidence interval, IC) per 1,000 all-cause hospitalizations in different age strata [< 6 years; 6-11 years and 12-17 years] were estimated. RESULTS: A total of 94,198 hospitalizations due to hepatic or infectious diseases with potential liver injury were analyzed. Of them, 1,535 children/adolescents [48.2% male sex, 41.6% aged < 6 years] were hospitalized with hepatitis with unknown etiology. The top ICD-10 codes were B19.9 [unspecified viral hepatitis without hepatic coma; 39.9% (n = 612)], K72.9 [hepatic failure, unspecified; 29.8% (n = 457)], and K72.0 [hepatic failure, not elsewhere classified; 14.5% (n = 223)]. A total of 8.5% (n = 131) of individuals required liver transplantation and 7.0% (n = 107) died during the hospital-stay. In 2021, the incidence rates (95% CI) of hospitalizations for hepatitis with unknown etiology were 7.80 (7.63-7.98), 17.96 (17.46-18.48) and 13.28 (12.95-13.62) per 1,000 all-cause hospitalizations in subjects aged < 6 years, 6-11 years and 12-17 years-old, respectively. Similarly, the incidence rates of hospitalization due to hepatitis with unknown etiology per 1,000 all-cause hospitalizations (CI95%) in January-February/2022 were 7.52 (7.11-7.94), 16.82 (15.68-18.03), and 13.96 (13.10-14.85) for children/adolescents with age < 6 years, 6-11 years, and 12-17 years, respectively. CONCLUSIONS: A non-negligible number of hospitalizations due to hepatitis with unknown etiology in children/adolescents was observed in the last years in Brazil. Up to 15% of those cases needed liver transplantation or died.

Inflammasome Genetic Variants Are Associated with Protection to Clinical Severity of COVID-19 among Patients from Rio de Janeiro, Brazil.

COVID-19 has a broad spectrum of clinical manifestations, from asymptomatic or mild/moderate symptoms to severe symptoms and death. The mechanisms underlying its clinical evolution are still unclear. Upon SARS-CoV-2 infection, host factors, such as the inflammasome system, are activated by the presence of the virus inside host cells. The search for COVID-19 risk factors is of relevance for clinical management. In this study, we investigated the impact of inflammasome single-nucleotide polymorphisms (SNPs) in SARS-CoV-2-infected individuals with distinct severity profiles at clinical presentation. Patients were divided into two groups according to disease severity at clinical presentation based on the WHO Clinical Progression Scale. Group 1 included patients with mild/moderate disease (WHO < 6; n = 76), and group 2 included patients with severe/critical COVID-19 (WHO ≥ 6; n = 357). Inpatients with moderate to severe/critical profiles were recruited and followed-up at Hospital Center for COVID-19 Pandemic - National Institute of Infectology (INI)/FIOCRUZ, RJ, Brazil, from June 2020 to March 2021. Patients with mild disease were recruited at Oswaldo Cruz Institute (IOC)/FIOCRUZ, RJ, Brazil, in August 2020. Genotyping of 11 inflammasome SNPs was determined by real-time PCR. Protection and risk estimation were performed using unconditional logistic regression models. Significant differences in NLRP3 rs1539019 and CARD8 rs2043211 were observed between the two groups. Protection against disease severity was associated with the A/A genotype (ORadj = 0.36; P = 0.032), allele A (ORadj = 0.93; P = 0.010), or carrier-A (ORadj = 0.45; P = 0.027) in the NLRP3 rs1539019 polymorphism; A/T genotype (ORadj = 0.5; P = 0.045), allele T (ORadj = 0.93; P = 0.018), or carrier-T (ORadj = 0.48; P = 0.029) in the CARD8 rs2043211 polymorphism; and the A-C-G-C-C (ORadj = 0.11; P = 0.018), A-C-G-C-G (ORadj = 0.23; P = 0.003), C-C-G-C-C (ORadj = 0.37; P = 0.021), and C-T-G-A-C (ORadj = 0.04; P = 0.0473) in NLRP3 genetic haplotype variants. No significant associations were observed for the other polymorphisms. To the best of our knowledge, this is the first study demonstrating an association between CARD8 and NLRP3 inflammasome genetic variants and protection against COVID-19 severity, contributing to the discussion of the impact of inflammasomes on COVID-19 outcomes.

Effectiveness of Direct-acting Agents After Liver Transplantation A Real-life Study in Rio de Janeiro.

BACKGROUND: Data concerning hepatitis C virus (HCV) treatment using direct-acting agents (DAAs) post liver transplantation (LT) remains scarce in low- and average-income countries. AIM OF THE STUDY: To evaluate the safety and efficacy of post-LT HCV treatment using DAAs in Rio de Janeiro (Brazil), and to assess the course of hepatic biomarkers after sustained virological response (SVR). METHODS: Data from LT recipients with recurrent HCV treated using DAAs was retrospectively analyzed. HCV was defined by detectable HCV-RNA with elevated aminotransferases and/or histological signs of infection on liver biopsy post LT. SVR was defined as undetectable HCV-RNA 12 weeks after the end of treatment. Aspartate-to-Platelet Ratio Index (APRI) and Fibrosis-4 score (FIB-4) were calculated before treatment and after SVR. RESULTS: 116 patients (63% male, median age 62 years, 75% genotype 1 and 62% with hepatocellular carcinoma [HCC] prior to LT) were included. Cirrhosis was identified in the allograft of 21 subjects (18%). The overall SVR was 96.6% without differences in SVR proportion according to clinical/demographic characteristics, genotype or presence of cirrhosis. SVR rates were similar in individuals with and without HCC pre-LT (95.8% [95% CI: 87.6-98.7] vs. 97.7% [95% CI: 85.0-99.7%], p = 0.588). No serious adverse events were observed and the use of ribavirin was associated with at least one adverse event (OR = 8.71 [95% CI: 3.17-23.99]). SVR was associated with regression of APRI (OR = 26.00 [95% CI 4.27-1065.94]) and FIB-4 (OR = 15.00 [95% CI: 2.30-631.47]). CONCLUSION: Post-LT HCV treatment with DAAs was safe and effective and associated with a significant decrease in hepatic biomarker levels after SVR.

Prevalence and predictors of anti-SARS-CoV-2 serology in a highly vulnerable population of Rio de Janeiro: A population-based serosurvey.

Background: COVID-19 serosurveys allow for the monitoring of the level of SARS-CoV-2 transmission and support data-driven decisions. We estimated the seroprevalence of anti-SARS-CoV-2 antibodies in a large favela complex in Rio de Janeiro, Brazil. Methods: A population-based panel study was conducted in Complexo de Manguinhos (16 favelas) with a probabilistic sampling of participants aged ≥1 year who were randomly selected from a census of individuals registered in primary health care clinics that serve the area. Participants answered a structured interview and provided blood samples for serology. Multilevel regression models (with random intercepts to account for participants' favela of residence) were used to assess factors associated with having anti-S IgG antibodies. Secondary analyses estimated seroprevalence using an additional anti-N IgG assay. Findings: 4,033 participants were included (from Sep/2020 to Feb/2021, 22 epidemic weeks), the median age was 39·8 years (IQR:21·8-57·7), 61% were female, 41% were mixed-race (Pardo) and 23% Black. Overall prevalence was 49·0% (95%CI:46·8%-51·2%) which varied across favelas (from 68·3% to 31·4%). Lower prevalence estimates were found when using the anti-N IgG assay. Odds of having anti-S IgG antibodies were highest for young adults, and those reporting larger household size, poor adherence to social distancing and use of public transportation. Interpretation: We found a significantly higher prevalence of anti-S IgG antibodies than initially anticipated. Disparities in estimates obtained using different serological assays highlight the need for cautious interpretation of serosurveys estimates given the heterogeneity of exposure in communities, loss of immunological biomarkers, serological antigen target, and variant-specific test affinity. Funding: Fundação Oswaldo Cruz, Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ), the European Union's Horizon 2020 research and innovation programme, Royal Society, Serrapilheira Institute, and FAPESP.

Agreement and accuracy of shear-wave techniques (point shear-wave elastography and 2D-shear-wave elastography) using transient elastography as reference.

OBJECTIVE: We aimed to evaluate the agreement/accuracy of point shear-wave elastography (p-SWE) and 2D-shear-wave elastography (2D-SWE) for liver fibrosis staging using transient elastography (TE) as the reference. METHODS: This retrospective study analyzed data from people with chronic liver diseases submitted to TE, p-SWE, and 2D-SWE. Liver fibrosis stages were defined using the TE's 'rule of five': normal (<5 kPa); suggestive of compensated-advanced chronic liver disease (cACLD) (10-15 kPa); highly suggestive of cACLD (15-20 kPa); suggestive of clinically significant portal hypertension (>20 kPa). Agreement and accuracy of p-SWE and 2D-SWE were assessed. Optimal cutoffs for p-SWE and 2D-SWE were identified using the point nearest to the upper left corner of the ROC curves. RESULTS: A total of 289 participants were included. The correlation between TE and 2D-SWE (rho = 0.59; P < 0.001) or p-SWE (rho = 0.69; P < 0.001) was satisfactory. The AUROCs (95% CI) of 2D-SWE and p-SWE for TE ≥ 5 kPa; TE ≥ 10 kPa; TE ≥ 15 kPa and TE ≥ 20 kPa were 0.757 (0.685-0.829) and 0.741 (0.676-0.806); 0.819 (0.770-0.868) and 0.870 (0.825-0.915); 0.848 (0.803-0.893) and 0.952 (0.927-0.978); 0.851 (0.806-0.896) and 0.951 (0.920-0.982), respectively. AUROCs of 2D-SWE were significantly lower compared with p-SWE for detecting cACLD. Optimal thresholds of 2D-SWE and p-SWE for TE ≥ 15 kPa were 8.82 kPa (sensitivity = 86% and specificity = 79%) and 8.86 kPa (sensitivity = 90% and specificity = 92%), respectively. CONCLUSION: LSM by p-SWE and 2D-SWE techniques were correlated with TE. LSM by p-SWE seems to be more accurate than 2D-SWE to identify patients with more advanced fibrosis.

In-hospital mortality and severe outcomes after hospital discharge due to COVID-19: A prospective multicenter study from Brazil.

Background: We evaluated in-hospital mortality and outcomes incidence after hospital discharge due to COVID-19 in a Brazilian multicenter cohort. Methods: This prospective multicenter study (RECOVER-SUS, NCT04807699) included COVID-19 patients hospitalized in public tertiary hospitals in Brazil from June 2020 to March 2021. Clinical assessment and blood samples were performed at hospital admission, with post-hospital discharge remote visits. Hospitalized participants were followed-up until March 31, 2021. The outcomes were in-hospital mortality and incidence of rehospitalization or death after hospital discharge. Kaplan-Meier curves and Cox proportional-hazard models were performed. Findings: 1589 participants [54.5% male, age=62 (IQR 50-70) years; BMI=28.4 (IQR,24.9-32.9) Kg/m² and 51.9% with diabetes] were included. A total of 429 individuals [27.0% (95%CI,24.8-29.2)] died during hospitalization (median time 14 (IQR,9-24) days). Older age [vs<40 years; age=60-69 years-aHR=1.89 (95%CI,1.08-3.32); age=70-79 years-aHR=2.52 (95%CI,1.42-4.45); age≥80-aHR=2.90 (95%CI 1.54-5.47)]; noninvasive or mechanical ventilation at admission [vs facial-mask or none; aHR=1.69 (95%CI 1.30-2.19)]; SAPS-III score≥57 [vs<57; aHR=1.47 (95%CI 1.13-1.92)] and SOFA score≥10 [vs <10; aHR=1.51 (95%CI 1.08-2.10)] were independently associated with in-hospital mortality. A total of 65 individuals [6.7% (95%CI 5.3-8.4)] had a rehospitalization or death [rate=323 (95%CI 250-417) per 1000 person-years] in a median time of 52 (range 1-280) days post-hospital discharge. Age ≥ 60 years [vs <60, aHR=2.13 (95%CI 1.15-3.94)] and SAPS-III ≥57 at admission [vs <57, aHR=2.37 (95%CI 1.22-4.59)] were independently associated with rehospitalization or death after hospital discharge. Interpretation: High in-hospital mortality rates due to COVID-19 were observed and elderly people remained at high risk of rehospitalization and death after hospital discharge. Funding: Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Programa INOVA-FIOCRUZ.

Frequency and predictive factors of minimal hepatic encephalopathy before and after sustained virological response in HCV cirrhosis.

Introduction: Data of minimal hepatic encephalopathy (MHE) before and after hepatitis C virus (HCV) treatment remain scarce. We aimed to describe the prevalence, evolution and predictive factors of MHE before and after a sustained virological response (SVR). Material and methods: It was a prospective study that included adults with cirrhosis due to HCV treated by direct-acting agents (DAA). MHE was assessed using the Psychometric Hepatic Encephalopathy Score (PHES). Results: 104 patients (65% female, age 60 ±10 years; 69% with diabetes, 47% with hypertension; 82% Child-Pugh A) were included. MHE was assessed just before therapy and 12 (IQR 7-15) months after SVR. Prevalence of MHE before HCV treatment and after SVR were 16% and 22%, respectively (p = 0.18). Resolution of MHE after SVR occurred in a few patients (n = 4/17) and 10 of 87 patients (11.5%) without MHE before treatment developed this condition after SVR. MHE after SVR was more common in patients with MHE before treatment (57% vs. 5%, p < 0.001). In multivariate analysis, older age, hypertension and hypoalbuminemia after treat-ment were predictors of MHE after SVR. In the absence of all these variables, none of the patients had MHE. In contrast, the prevalence of MHE was 42% and 70% in the case of presence of any 2 of these factors and all these conditions, respectively. Conclusions: MHE is frequent in patients with cirrhosis who achieved SVR after DAA. SVR is associated with low probability of resolution of MHE and may not entirely protect patients from developing de novo MHE. Presence of MHE before DAA, older age, hypertension and hypoalbuminemia after SVR were independently associated with this condition.

A pilot study of microbial signatures of liver disease in those with HIV mono-infection in Rio de Janeiro, Brazil.

OBJECTIVE: The rectal microbiome was examined to assess the relationship between the microbiome and liver disease in HIV-infection. DESIGN: Eighty-two HIV-1 mono-infected individuals from the PROSPEC-HIV-study (NCT02542020) were grouped into three liver health categories based on results of controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) of transient elastography: normal (n = 30), steatosis (n = 30), or fibrosis (n = 22). METHODS: Liver steatosis and fibrosis were defined by CAP at least 248 dB/m and LSM at least 8.0 kPa, respectively. 16S rRNA gene and whole genome shotgun metagenomic sequencing were performed on rectal swabs. Bacterial differences were assessed using zero-inflated negative binomial regression and random forests modeling; taxonomic drivers of functional shifts were identified using FishTaco. RESULTS: Liver health status explained four percentage of the overall variation (r2 = 0.04, P = 0.003) in bacterial composition. Participants with steatosis had depletions of Akkermansia muciniphila and Bacteroides dorei and enrichment of Prevotella copri, Finegoldia magna, and Ruminococcus bromii. Participants with fibrosis had depletions of Bacteroides stercoris and Parabacteroides distasonis and enrichment of Sneathia sanguinegens. In steatosis, functional analysis revealed increases in primary and secondary bile acid synthesis encoded by increased Eubacterium rectale, F. magna, and Faecalibacterium prausnitzii and decreased A. muciniphila, Bacteroides fragilis and B. dorei. Decreased folate biosynthesis was driven by similar changes in microbial composition. CONCLUSION: HIV mono-infection with steatosis or fibrosis had distinct microbial profiles. Some taxa are similar to those associated with non-alcoholic fatty liver disease in HIV-negative populations. Further studies are needed to define the role of the gut microbiota in the pathogenesis of liver disease in HIV-infected persons.

Hepatitis of unknown etiology in children in Brazil: A new challenge or the usual scenario ?

ABSTRACT Background: An outbreak of acute hepatitis of unknown etiology in children was recently reported worldwide. We aimed to describe the burden of hospitalizations due to hepatitis of unknown etiology in children/adolescents in Brazilian public hospitals. Methods: We retrieved a database of all hospitalizations in the Brazilian Unified Health System (SUS) from January/2019 to February/2022 using the "microdatasus" R package. Hepatitis of unknown etiology was defined by the following International Classification of Diseases [ICD-10] codes: B19, B19.0, B19.9, K72.0, K72.9, K75, K75.9, R94.5, or R93.2. The incidence rates (95% confidence interval, IC) per 1,000 all-cause hospitalizations in different age strata [< 6 years; 6-11 years and 12-17 years] were estimated. Results: A total of 94,198 hospitalizations due to hepatic or infectious diseases with potential liver injury were analyzed. Of them, 1,535 children/adolescents [48.2% male sex, 41.6% aged < 6 years] were hospitalized with hepatitis with unknown etiology. The top ICD-10 codes were B19.9 [unspecified viral hepatitis without hepatic coma; 39.9% (n = 612)], K72.9 [hepatic failure, unspecified; 29.8% (n = 457)], and K72.0 [hepatic failure, not elsewhere classified; 14.5% (n = 223)]. A total of 8.5% (n = 131) of individuals required liver transplantation and 7.0% (n = 107) died during the hospital-stay. In 2021, the incidence rates (95% CI) of hospitalizations for hepatitis with unknown etiology were 7.80 (7.63-7.98), 17.96 (17.46-18.48) and 13.28 (12.95-13.62) per 1,000 all-cause hospitalizations in subjects aged < 6 years, 6-11 years and 12-17 years-old, respectively. Similarly, the incidence rates of hospitalization due to hepatitis with unknown etiology per 1,000 all-cause hospitalizations (CI95%) in January-February/2022 were 7.52 (7.11-7.94), 16.82 (15.68-18.03), and 13.96 (13.10-14.85) for children/adolescents with age < 6 years, 6-11 years, and 12-17 years, respectively. Conclusions: A non-negligible number of hospitalizations due to hepatitis with unknown etiology in children/adolescents was observed in the last years in Brazil. Up to 15% of those cases needed liver transplantation or died.

Relationship between Dietary Fatty Acid Intake with Nonalcoholic Fatty Liver Disease and Liver Fibrosis in People with HIV.

We aimed to evaluate the relationship between food intake of lipids with nonalcoholic fatty liver disease (NAFLD) and/or liver fibrosis in people living with HIV/AIDS (PLWHA). In this cross-sectional study, transient elastography was used to detect the presence of NAFLD and/or liver fibrosis. The dietary intake of fats and fatty acids (FA) were assessed by two 24 h dietary recalls (24-HDR) (n = 451). Multivariate logistic regression models were performed. Participants with higher intake of total fat were associated with higher odds for NAFLD compared to those with lower consumption [adjusted odds ratio (aOR) = 1.91 (95% confidence interval (95% CI) 1.06-3.44)]. Furthermore, participants with intermediate intake of n6-PUFA (n6-poly-unsaturated FA) and lauric FA had lower odds for NAFLD, respectively aOR = 0.54 (95% CI 0.3-0.98) and aOR = 0.42 (95% CI 0.22-0.78). Additionally, a higher intake of myristoleic FA (fourth quartile) was a significant protective factor for NAFLD [aOR = 0.56 (95% CI 0.32-0.99)]. Participants with higher intake of lauric FA [0.38 (95% CI 0.18-0.80)], myristic FA [0.38 (0.17-0.89)], palmitoleic FA [0.40 (0.19-0.82)] and oleic FA [0.35 (0.16-0.79)] had positively less odds of having liver fibrosis. On the other hand, higher intake of n-6 PUFA was significantly associated with fibrosis [aOR = 2.45 (95% CI 1.12-5.32)]. Dietary assessment of total fat and FA should be incorporated into HIV care as a tool for preventing NAFLD and fibrosis in PLWHA.

Liver stiffness regression after sustained virological response by direct-acting antivirals reduces the risk of outcomes.

The role of liver stiffness measurement (LSM) after sustained virological response (SVR) in HCV patients treated by direct-acting antivirals (DAAs) remains unclear. We aimed to evaluate LSM regression value after SVR and to identify risk factors associated with liver related complications (LRC) or death. This retrospective study analyzed patients with LSM ≥ 10 kPa with LSM by transient elastography pre-DAAs and post-SVR. Patients with previous hepatic decompensation were excluded. Medical records were reviewed to identify primary outcomes. Kaplan-Meier curves and time-to-event Cox proportional-hazard models were performed. 456 patients [65% female, 62 years (IQR 57-68)] were included. During a follow-up of 2.3 years (IQR 1.6-2.7), 28 patients developed 37 outcomes [rate = 29.0 (95% CI 20.0-42.0) per 1000 person-years]. The cumulative incidence of outcomes was significantly lower in patients who regressed LSM ≥ 20% [3.4% (95% CI 1.8-7.0) vs. 9.0% (5.5-14.5), p = 0.028]. In a multivariate Cox-model [HR(95% CI)], male gender [HR = 3.00 (1.30-6.95), p = 0.010], baseline albumin < 3.5 mg/dL [HR = 4.49 (1.95-10.34), p < 0.001] and baseline unfavorable Baveno-VI [HR = 4.72 (1.32-16.83), p = 0.017] were independently associated and LSM regression ≥ 20% after SVR had a trend to reduce the risk of LRC or death [HR = 0.45 (0.21-1.02), p = 0.058]. The use of simple parameters before DAAs and repetition of LSM post-SVR can identify patients with different risks for severe outcome after HCV eradication.