Mechanisms of Accelerated Liver Fibrosis Progression during HIV Infection

Abstract Wit

Evaluation of rapid diagnostic tests for assessment of hepatitis B in resource-limited settings

Chronic Hepatitis B (HBV) is the most important cause of liver disease worldwide. There is a need for low-cost tests to aid in diagnosis and management of HBV infection in resource-limited settings. We evaluated the utility of several rapid diagnostic tests (RDT) in three different continents (Europe, South America, Africa). The HBsAg RDT showed optimal sensitivity and specificity. The anti-HBeAb RDT showed acceptable sensitivity and excellent specificity. Our results suggest that these RDTs could be used for screening and management of HBV.Fil: Leathers, James S.. Uc Davis School Of Medicine; Estados UnidosFil: Pisano, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; ArgentinaFil: Ré, Viviana Elizabeth. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Van Oord, Gertine. Erasmus MC. Department of Gastroenterology and Hepatology; Países BajosFil: Sultan, Amir. Addis Ababa University; EtiopíaFil: Boonstra, Andre. Erasmus MC. Department of Gastroenterology and Hepatology; Países BajosFil: Debes, Jose D.. University of Minnesota; Estados Unidos. Erasmus MC. Department of Gastroenterology and Hepatology; Países Bajo

Validation of a point-of-care rapid diagnostic test for hepatitis C for use in resource-limited settings

Treatment of HCV with direct-acting antivirals has enabled the discussion of HCV eradicationworldwide. Envisioning this aim requires implementation of mass screening in resource-limited areas, usuallyconstrained by testing costs. We validated a low-cost, rapid diagnosis test (RDT) for HCV in three different continents in 141individuals. The HCV RDT showed 100% specificity and sensitivity across different samples regardless of genotypeor viral load (in samples with such information, 90%). The HCV test validated in this study can allow for HCV screening in areas of need when properly used.Fil: Leathers, James S.. Vanderbilt University; Estados UnidosFil: Pisano, María Belén. Universidad Nacional de Cordoba. Facultad de Medicina. Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ré, Viviana Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Instituto de Virología; ArgentinaFil: van Oord, Gertine. Erasmus Medical Center; Países BajosFil: Sultan, Amir. Addis Ababa University; EtiopíaFil: Boonstra, Andre. Erasmus Medical Center; Países BajosFil: Debes, Jose D.. Universidad de Minnesota; Estados Unido

Assessment of <i>TLL1 </i>variant and risk of hepatocellular carcinoma in Latin Americans and Europeans

Introduction and Objectives: Tolloid like protein 1 (TLL1) rs17047200 has been reported to be associated with HCC development and liver fibrosis. However, to our knowledge, no studies have been performed on Latin Americans and comparative differences between TLL1 rs17047200 in HCC patients from Latin America and Europe are undefined. Materials and Methods: Cross-sectional analysis performed on Latin American and European individuals. We analyzed TLL1 rs17047200 on DNA from 1194 individuals, including 420 patients with HCC (86.0 % cirrhotics) and 774 without HCC (65.9 % cirrhotics). Results: TLL1 rs17047200 genotype AT/TT was not associated with HCC development in Latin Americans (OR: 0.699, 95 %CI 0.456-1.072, p = 0.101) or Europeans (OR: 0.736, 95 %CI 0.447-1.211, p = 0.228). TLL1 AT/TT was not correlated with fibrosis stages among metabolic dysfunction-associated steatotic liver disease (MASLD) patients from Latin America (OR: 0.975, 95 %CI 0.496-1.918, p = 0.941). Among Europeans, alcohol-related HCC had lower TLL1 AT/TT frequencies than cirrhosis (18.3 % versus 42.3 %, OR: 0.273, 95 %CI 0.096-0.773, p = 0.015). Conclusions: We found no evidence that the TLL1 rs17047200 AT/TT genotype is a risk factor for HCC development in Latin Americans or Europeans. A larger study integrating ethnic and etiology backgrounds is needed to determine the importance of the TLL1 SNP in HCC development.</p

Prevalence and risk of hepatitis E virus infection in the HIV population of Nepal

Background: Infection with the hepatitis E virus (HEV) can cause acute hepatitis in endemic areas in immune-competent hosts, as well as chronic infection in immune-compromised subjects in non-endemic areas. Most studies assessing HEV infection in HIV-infected populations have been performed in developed countries that are usually affected by HEV genotype 3. The objective of this study is to measure the prevalence and risk of acquiring HEV among HIV-infected individuals in Nepal. Methods: We prospectively evaluated 459 Human Immunodeficiency Virus (HIV)-positive individuals from Nepal, an endemic country for HEV, for seroprevalence of HEV and assessed risk factors associated with HEV infection. All individuals were on antiretroviral therapy and healthy blood donors were used as controls. Results: We found a high prevalence of HEV IgG (39.4%) and HEV IgM (15.3%) in HIV-positive subjects when compared to healthy HIV-negative controls: 9.5% and 4.4%, respectively (OR: 6.17, 95% CI 4.42-8.61, p \u3c 0.001 and OR: 3.7, 95% CI 2.35-5.92, p \u3c 0.001, respectively). Individuals residing in the Kathmandu area showed a significantly higher HEV IgG seroprevalance compared to individuals residing outside of Kathmandu (76.8% vs 11.1%, OR: 30.33, 95% CI 18.02-51.04, p = 0.001). Mean CD4 counts, HIV viral load and presence of hepatitis B surface antigen correlated with higher HEV IgM rate, while presence of hepatitis C antibody correlated with higher rate of HEV IgG in serum. Overall, individuals with HEV IgM positivity had higher levels of alanine aminotransferase (ALT) than IgM negative subjects, suggesting active acute infection. However, no specific symptoms for hepatitis were identified. Conclusion: HIV-positive subjects living in Kathmandu are at higher risk of acquiring HEV infection as compared to the general population and to HIV-positive subjects living outside Kathmandu

MBOAT7 rs641738 Variant Is Not Associated with an Increased Risk of Hepatocellular Carcinoma in a Latin American Cohort

Background: The rs641738 C &gt; T single-nucleotide polymorphism of MBOAT7 has been associated with hepatocellular carcinoma (HCC) and nonalcoholic fatty liver disease (NAFLD). Latin Americans have high rates of HCC and NAFLD, but no assessment between MBOAT7 and HCC has been performed in this population. Aims: We provide the first assessment of the impact of MBOAT7 on HCC risk in Latin Americans. Methods: Patients were prospectively recruited into the ESCALON network, designed to collect samples from Latin American patients with HCC in 6 South American countries (Argentina, Ecuador, Brazil, Chile, Peru, and Colombia). A European cohort and the general Hispanic population of gnomAD database were included for comparison. Associations between HCC and MBOAT7 were evaluated using logistic regression. Results:In total, 310 cases of HCC and 493 cases of cirrhosis without HCC were assessed. The MBOAT7 TT genotype was not predictive of HCC in Latin Americans (TT vs CC OR adjusted = 1.15, 95% CI 0.66–2.01, p = 0.610) or Europeans (TT vs CC OR adjusted = 1.20, 95% CI 0.59–2.43, p = 0.621). No significant association was noted on subgroup analysis for NAFLD, viral hepatitis, or alcohol-related liver disease. The TT genotype was increased in the NAFLD-cirrhosis cohort of Latin Americans compared to a non-cirrhotic NAFLD cohort (TT vs CC + CT OR = 2.75, 95% CI 1.10–6.87, p = 0.031). Conclusion: The rs631738 C &gt; T allele of MBOAT7 was not associated with increased risk of HCC in Latin Americans or Europeans. An increase in the risk of cirrhosis was noted with the TT genotype in Latin Americans with NAFLD. Graphical Abstract: [Figure not available: see fulltext.]</p

Reconciling Deep Calibration and Demographic History: Bayesian Inference of Post Glacial Colonization Patterns in Carcinus aestuarii (Nardo, 1847) and C. maenas (Linnaeus, 1758)

A precise inference of past demographic histories including dating of demographic events using Bayesian methods can only be achieved with the use of appropriate molecular rates and evolutionary models. Using a set of 596 mitochondrial cytochrome c oxidase I (COI) sequences of two sister species of European green crabs of the genus Carcinus (C. maenas and C. aestuarii), our study shows how chronologies of past evolutionary events change significantly with the application of revised molecular rates that incorporate biogeographic events for calibration and appropriate demographic priors. A clear signal of demographic expansion was found for both species, dated between 10,000 and 20,000 years ago, which places the expansions events in a time frame following the Last Glacial Maximum (LGM). In the case of C. aestuarii, a population expansion was only inferred for the Adriatic-Ionian, suggestive of a colonization event following the flooding of the Adriatic Sea (18,000 years ago). For C. maenas, the demographic expansion inferred for the continental populations of West and North Europe might result from a northward recolonization from a southern refugium when the ice sheet retreated after the LGM. Collectively, our results highlight the importance of using adequate calibrations and demographic priors in order to avoid considerable overestimates of evolutionary time scales

Analysis of Genetic Linkage of HIV From Couples Enrolled in the HIV Prevention Trials Network 052 Trial

Background. The HIV Prevention Trials Network (HPTN) 052 trial demonstrated that early initiation of antiretroviral therapy (ART) reduces human immunodeficiency virus (HIV) transmission from HIV-infected adults (index participants) to their HIV-uninfected sexual partners. We analyzed HIV from 38 index-partner pairs and 80 unrelated index participants (controls) to assess the linkage of seroconversion events