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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 was 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. [ABSTRACT FROM AUTHOR]

Background Patients with chronic hepatitis C virus (HCV) do not respond to hepatitis B virus (HBV) vaccination as efficiently as the general population. We assessed if revaccination after HCV treatment resulted in improved response. Methods Previous HBV vaccine nonresponders were prospectively recruited for revaccination after HCV eradication. Hepatitis B surface antibody (HBsAb) testing was performed 1 month after series completion. Results Follow-up HBsAb testing was performed in 31 of 34 enrolled patients with 21 (67.7%) reactive results. There were no significant differences in HBsAb reactivity based on age, sex, race, or advanced fibrosis presence. Conclusions HBV vaccine nonresponders should be considered for revaccination following HCV cure. [ABSTRACT FROM AUTHOR]

Background: The rs641738 C > 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 > 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. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatocellular carcinoma (HCC) is a prevalent and fatal type of liver cancer with various risk factors. This study examines the connection between a specific genetic variant, STAT4 rs7574865, and HCC risk in Latin American and European populations. The results reveal no general association between this genetic variant and HCC in the studied groups. This study underscores the significance of researching diverse populations to gain a better understanding of the broader influence of genetic factors on HCC risk, which may aid in developing more effective strategies for identifying and managing high-risk individuals. Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. The STAT4 rs7574865 genetic variant has been associated with an increased risk of developing HCC in Asian populations. However, this association has not been studied in Latin America and is poorly assessed in European populations. This case-control study investigated the association between STAT4 rs7574865 and HCC risk in these populations. We evaluated DNA samples from seven medical institutions across six Latin American countries and one Dutch institution in 1060 individuals (344 HCC and 716 controls). STAT4 rs7574865 SNP was genotyped using TaqMan-genotyping assay and analyzed using logistic regression. We found no significant association between the homozygous risk allele (G) of STAT4 and HCC development in either population, with odds ratios (OR) for GG versus TT of 0.85 (CI: 0.48–1.52, p = 0.58) and 0.81 (CI: 0.34–1.93, p = 0.67) for Latin Americans and Europeans respectively. No correlation was found between the risk allele and HCC based on underlying liver disease. However, we found that Latin Americans of European ancestry were more likely to carry the risk allele. Our results suggest that the STAT4 SNP rs7574865 does not influence the risk of developing HCC in Latin American or European populations, highlighting the importance of evaluating genetic risk factors in various ethnic groups and understanding the possible influence of ancestry on the genetic basis of disease. [ABSTRACT FROM AUTHOR]

Summary: Background: The burden of non‐alcoholic fatty liver disease (NAFLD) in South America is among the highest in the world. However, the epidemiology and risk factors for NAFLD are insufficiently described in the region. Aim: To explore the associations between clinical characteristics and histopathological features of NAFLD Methods: This was a descriptive study of 2722 patients with NAFLD from 8 medical centres across 5 South American countries. We collected clinical, biochemical and histopathological data using a templated chart. Fibrosis was assessed by elastography or fibrosis scores and confirmed with biopsy when available. We examined associations between histopathological features and clinical characteristics with logistic regression models. Models were adjusted for country, age and sex. Results: The median age was 53 years (IQR: 41–62), and 63% were women. Subjects from Brazil had the highest body mass index at 42 kg/m2. Sixty‐seven percent had dyslipidemia, 46% had obesity, 30% had hypertension, 17% had type 2 diabetes mellitus (T2DM) and 34% had metabolic syndrome. Biopsy reports were available for 948 (35%), of which 58% showed fibrosis, 91% steatosis and 65% inflammation; 25% showed significant fibrosis and 27% severe steatosis. Metabolic syndrome, T2DM and hypertension were significantly associated with significant fibrosis (OR = 1.94, p < 0.001; OR = 2.93, p < 0.001 and OR = 1.60, p = 0.003, respectively), severe steatosis (OR = 2.05, p < 0.001; OR = 1.91, p = 0.001 and OR = 2.17, p < 0.001, respectively) and liver inflammation (OR = 1.66, p = 0.007; OR = 2.00, p = 0.002; OR = 1.62, p = 0.001, respectively). Conclusions: In the largest NAFLD cohort study to date from South America, metabolic syndrome, hypertension and T2DM were independently associated with significant fibrosis, severe steatosis, and inflammation. The prevalence of T2DM was lower than the reported global prevalence. [ABSTRACT FROM AUTHOR]

Introduction and Objectives: Most epidemiological data on hepatocellular carcinoma (HCC) originate from resource-rich countries. We have previously described the epidemiology of HCC in South America through the South American Liver Research Network. Here, we provide an update on the changing epidemiology of HCC in the continent seven years since that report. Materials and Methods: We evaluated all cases of HCC diagnosed between 2019 to 2021 in centers from six countries in South America. A templated, retrospective chart review of patient characteristics at the time of HCC diagnosis, including basic demographic, clinical and laboratory data, was completed. Diagnosis of HCC was made radiologically or histologically for all cases via institutional standards. Results: Centers contributed to a total of 339 HCC cases. Peru accounted for 37% (n=125) of patients; Brazil 16% (n=57); Chile 15% (n=51); Colombia 14% (n=48); Argentina 9% (n=29); and Ecuador 9% (n=29). The median age at HCC diagnosis was 67 years (IQR 59-73) and 61% were male. The most common risk factor was nonalcoholic fatty liver disease (NAFLD, 37%), followed by hepatitis C (17%), alcohol use disorder (11%) and hepatitis B (12%). The majority of HCCs occurred in the setting of cirrhosis (80%). HBV-related HCC occurred at a younger age compared to other causes, with a median age of 46 years (IQR 36-64). Conclusions: We report dramatic changes in the epidemiology of HCC in South America over the last decade, with a substantial increase in NAFLD-related HCC. HBV-related HCC still occurs at a much younger age when compared to other causes. [ABSTRACT FROM AUTHOR]

The article offers information on the global impact of Hepatitis C virus (HCV) as a major cause of morbidity and mortality. Topics include the prevalence of HCV worldwide, particularly in Latin America where millions of individuals live with HCV, with a significant proportion experiencing advanced fibrosis or cirrhosis.

Background: COVID-19 is associated with higher morbidity and mortality in patients with chronic liver diseases (CLDs). However, our understanding of the long-term outcomes of COVID-19 in patients with CLD is limited. Methods: We conducted a multicenter, observational cohort study of adult patients with CLD who were diagnosed with COVID-19 before May 30, 2020, to determine long-term clinical outcomes. We used a control group of patients with CLD confirmed negative for COVID-19. Results: We followed 666 patients with CLD (median age 58 years, 52.8% male) for a median of 384 (interquartile range: 31-462) days. The long-term mortality was 8.1%; with 3.6% experiencing delayed COVID-19-related mortality. Compared to a propensity-matched control group of patients with CLD without COVID-19 (n= 1332), patients with CLD with COVID-19 had worse long-term survival [p< 0.001; hazards ratio (HR): 1.69; 95% CI: 1.19-2.41] and higher rate of hospitalization (p< 0.001, HR: 2.00, 1.62-2.48) over a 1-year follow-up period. Overall, 29.9% of patients reported symptoms of long-COVID-19. On multivariable analysis, female sex (p= 0.05, HR: 2.45, 1.01-2.11), Hispanic ethnicity (p =0.003, HR: 1.94, 1.26-2.99), and severe COVID-19 requiring mechanical ventilation (p =0.028, HR: 1.74, 1.06-2.86) predicted long-COVID-19. In survivors, liver-related laboratory parameters showed significant improvement after COVID-19 resolution. COVID-19 vaccine status was available for 72% (n =470) of patients with CLD and history of COVID-19, of whom, 70% (n =326) had received the COVID-19 vaccine. Conclusions: Our large, longitudinal, multicenter study demonstrates a high burden of long-term mortality and morbidity in patients with CLD and COVID-19. Symptoms consistent with long-COVID-19 were present in 30% of patients with CLD. These results illustrate the prolonged implications of COVID-19 both for recovering patients and for health care systems. [ABSTRACT FROM AUTHOR]

Simple Summary: Chronic liver diseases commonly cause severe scarring of the liver (cirrhosis) and liver cancer. The eventual progression of this scarring process to liver cancer is influenced by a variety of factors, including inflammatory cytokines (soluble mediators of cell communication). In order to increase our understanding of these mediators we studied them in the blood of patients with hepatitis B (HBV), hepatitis C (HCV), alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) patients with liver cirrhosis. We studied more than a 100 cytokines in up to 400 patients. We discovered that patients with cirrhosis had a vast upregulation of a wide variety of immune mediators, which stimulated inflammation and were linked with tumor-promoting roles. In contrast to prevailing assumptions, each type of underlying liver disease exhibited a unique immune mediator profile in blood, which is likely to impact how we will study these markers in the future. Patients with HBV cirrhosis had the largest number of upregulated inflammation-inducing mediators, compared to HCV, ALD and NAFLD. Next, we related blood immune mediator levels with liver cancer. To do so, we studied cytokine profiles in patients with small tumors, thus, those qualified for surgical curative strategies. We observed unique sets of cytokines in serum in each liver cancer group, indicating a role for these mediators in detecting liver cancer. In conclusion, our findings underscore the impact of different liver diseases on circulating immune mediators. Future studies that aim to study them as diagnostic tools will need to correct for this important effect accordingly. Background and Aims: Chronic liver disease—from any etiology—can progress to fibrosis, cirrhosis and hepatocellular carcinoma (HCC). The progression of liver cirrhosis to the end stages of disease is influenced by a variety of factors, including inflammatory cytokines. We pursued a study of cytokine-mediated inflammatory responses in hepatitis B (HBV), hepatitis C (HCV), alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) patients with liver cirrhosis. Methods: Immune profiles were determined through the serum multiplex profiling of >100 cytokines in a 188 cirrhotic patients, 35 healthy controls and 196 early-stage HCC patients. Results: Patients with liver cirrhosis exhibited a vast upregulation of proinflammatory cytokines (p < 0.0001), including those with pro-oncogenic features, when compared to healthy individuals. In contrast to prevailing assumptions, each etiological cause of cirrhosis exhibited a unique cytokine profile in blood. Regardless of antiviral therapy, HBV cirrhosis patients had the largest number of upregulated proinflammatory mediators, compared to HCV, ALD and NAFLD (p < 0.0001). To further evaluate the etiology-dependent modulation of cytokine response in relation to liver cancer, we studied cytokine profiles in early-stage HCC patients strictly stratified by underlying liver disease. We observed unique sets of differentially expressed cytokines in each cohort of early-stage HCC patients of different cirrhosis etiologies. Conclusions: Our findings, therefore, underscore the importance of stratification by the etiological cause of liver cirrhosis in immune-based studies. [ABSTRACT FROM AUTHOR]

Inactive carrier phases in chronic hepatitis B virus (HBV) infection present minimal liver disease and HBV replication activity suggesting partial immune reconstitution, although the mechanisms responsible remain elusive. Moreover, hepatitis B surface antigen (HBsAg) production-hypothesized to modulate the immune response-is unaltered. In the current study, we assessed the intrahepatic transcriptome in inactive carriers of HBV versus healthy liver donors, including in the context of diverse HBsAg levels (serum and liver), to better understand the phenomenon of immune control. We found a deregulated liver transcriptome in inactive carriers compared with healthy controls, despite normal liver function. Moreover, diverse HBsAg levels have minimal impact on the liver transcriptome in inactive carriers, although gene correlation analysis revealed that leukocyte activation, recruitment, and innate responses genes were correlated with liver HBsAg levels. These findings provide more insight into the mechanisms underlying anti-HBV strategies currently under development, aimed at interfering with HBsAg production or inducing a state of immune control. [ABSTRACT FROM AUTHOR]

Some studies have exposed an increase in liver cirrhosis in hepatitis E seropositive individuals living with human immunodeficiency virus. The interrelation between HEV seroprevalence and risk of liver disease in immune‐competent individuals remains under‐ investigated. Using the National Health and Nutrition Examination Survey (NHANES) data containing >30,000 subjects, we addressed if HEV exposure leads to subclinical effects that can influence liver health. We determined the association between HEV IgM and ALT and that of HEV IgG and Fib‐4—a composite score reflecting potential liver fibrosis. These analyses were repeated in populations at risk for liver disease as well as among different races and ethnicities. The prevalence of HEV IgG was significantly associated with age as IgG positive individuals were, on average, 20 years older than IgG negative patients. We found a statistically significant increase in the likelihood of having a Fib‐4 score >1.45 (significant fibrosis) in those positive for HEV IgG (RR: 1.03; 95% CI: 1.01–1.05). However, due to the small effect, it is unlikely that this association has clinical significance. Moreover, the effect was not present in those with pre‐existing liver disease. We found no association between ALT levels and the presence of HEV IgM or IgG. This is the first study examining subclinical effects of HEV infection in the United States. Our study found that in the general US population, predominantly asymptomatic HEV infections do not contribute to the overall burden of liver disease. [ABSTRACT FROM AUTHOR]

COVID-19 is now impacting every country in Africa and healthcare workers (HCWs) across the continent remain susceptible to professional burnout. We designed a 43-question survey addressing multiple aspects of the COVID-19 pandemic. The survey was anonymous, distributed via email and phone messaging to 13 countries in Africa. We obtained 489 analyzable responses. 49% off HCWs reported a decrease in income, with the majority experiencing between 1–25% salary reduction. Sixty-six percent reported some access to personal protective equipment (PPE), 20% had no access to PPE and only 14% reported proper access. Strikingly, the percentage reporting never feeling depressed changed from 61% before the pandemic to 31% during the pandemic, with an increase in daily depression from 2% to 20%. We found no association between depression and change in income, household size, availability of PPE or lockdown. Safety concerns related to stigma from being HCWs affected 56% of respondents. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus (HBV) infection disproportionally affects populations in subSaharan Africa. Lack of HBV awareness perpetuates disease burden in Africa. Objective: To promote HBV awareness in Tanzania using a systematic, measurable, and expandable approach to educating health care workers (HCW). Methods: We designed and implemented an HBV knowledge and teaching skills session in southern Tanzania to empower HCWs in leading education to promote disease awareness in their communities. Training was divided into two sessions: didactic and practical. A fivequestion anonymous survey was distributed in person immediately before and after the practical portion of the training to evaluate HBV knowledge as well as specific skills for teaching. Differences between responses before and after the sessions were evaluated by Chi-Square analysis. A sub-group of questions were further analyzed for differences based on HCW self-report of HBV serostatus awareness. Findings: 130 HCWs participated in the didactic lecture and 30 HCWs participated in both portions. A pre-post training five-question survey showed an increase in correct answers for all questions, with two showing statistical significance: HBV is silent (7% pre vs. 87% post; p < 0.0001), and repetition as key to promote awareness (63% pre vs. 100% post; p = 0.0002). Conclusions: Our low-cost intervention is applicable to increase HBV awareness in low resource settings across Africa. [ABSTRACT FROM AUTHOR]

Problem: We investigated if the PROGINS mutation increases the risk of hepatitis E virus (HEV) infection in liver transplant recipients. PROGINS was analyzed through KASP assay; HEV serologies assessed via enzyme‐linked immunosorbent assay and multiplex cytokine assays were evaluated in plasma with the ProcartaPlex human immunoassay. Seventy liver transplant recipients were evaluated, of which 23 (33%) were HEV immunoglobuln G (IgG)‐positive (HEV+). The frequency of PROGINS in the HEV+ group was 34%, compared with 14% in those that were HEV IgG negative (HEV−). Cytokine measurements in a sub‐set of samples from HEV+/PROGINS+ individuals showed decreased plasma levels of monokine induced by gamma interferon, a proliferation‐inducing ligand, and stem cell factor, as well as increased levels of eotaxin‐3 and interleukin‐31 compared with those HEV−/PROGINS− samples. Our findings suggest an association between the PROGINS mutation and seropositivity for HEV in liver transplant recipients with consequent distorted cytokine levels. Highlights: It is unclear why transplant recipients have an increased risk of HEV infection. We found an increased rate the PROGINS mutations liver transplant in HEV‐positive individuals. [ABSTRACT FROM AUTHOR]

To evaluate the characteristics and response to therapy for HCC in sub-Saharan Africa. We retrospectively evaluated demographic, clinical and outcome variables of HCC in a referral clinic in Ethiopia from 2016 to 2018. Survival assessment was performed using the Mann-Whitney test. Associations between categorical variables was assessed using Pearson Chi-square test. We report 46 HCC cases with a median age of 54 years (IQR 45–62) and 50% female. Viral hepatitis was the most common underlying etiology, with 41% of subjects infected with hepatitis B virus (HBV) and 45% with hepatitis C. The median MELD was 12 (IQR 8–17), we found no association between survival and a MELD score 15, regardless of underlying disease (pr=0.61, p>0.05). 31% of individuals underwent supportive treatment with a median survival of 27 days (IQR 19–181), 18% used Sorafenib (median survival of 94 days, IQR 24–121), and trans-arterial chemoembolization (TACE) was utilized in 16% (median survival of 352 days, IQR 30–436). HBV cases were diagnosed younger (31% before the age of 40) and those on Tenofovir had a longer median survival than those off Tenofovir (121 vs 34 days). Our study found that antiviral treatment of HBV infection was associated with longer survival in HCC. Furthermore, Sorafenib seemed beneficial in patients that used this modality and NLR was a good prognostic factor. [ABSTRACT FROM AUTHOR]

Background: Previous reports show conflicting results regarding hepatitis B virus (HBV) vaccine efficacy in Hepatitis C virus (HCV)-infected individuals. Aims: To evaluate HBV-vaccine response and identify possible factors that may contribute to lower vaccine efficacy in patients infected with HCV. Methods: We retrospectively evaluated all patients with chronic HCV infection at Hennepin County Medical Center, in Minneapolis, Minnesota, between 2002 and 2018. We addressed laboratory, liver-related, virus-related as well as vaccine-related variables, and their association to HBV vaccine response. Differences were tested using either a Chi-squared test or a T test to compare means between the two populations. Multivariate regression was modeled as a logistic regression. Results: 1506 patients were evaluated, of which 525 received appropriate HBV vaccination and were assessed for response. Among those, 79% were vaccine responders and 21% were non-responders. On multivariate analysis, cirrhosis was associated with lower response to the vaccine (OR 0.6, CI 0.44–0.94). We found no significant differences for vaccine response in relation to smoking (87% vs 86%), IV drug abuse (74% vs 72%), Diabetes Mellitus (26% vs 22%) being on hemodialysis (2% vs.5%), or virus related variables. Conclusion: HCV infection seems to impair HBV vaccine response, with cirrhosis being the only identifiable risk factor for hypo-responsiveness among studied clinical and virus-related variables. [ABSTRACT FROM AUTHOR]

Abstract: Background and Aims: Infection with Hepatitis E virus (HEV) can cause chronic liver disease in immunocompromised hosts. In transplant recipients, the use of certain immunosuppressants and food habits has been proposed as risk factors for HEV. In individuals infected with the human immunodeficiency virus (HIV), risk factors for HEV infection are less clear. We aimed to study the association between a mutation in the progesterone receptor (PR) named PROGINS and HEV‐infected in HIV‐positive individuals. Methods: We evaluated the presence of the SNP PROGINS via KASP in serum samples of 64 HIV‐positive individuals and 187 healthy controls. We performed ELISA tests to address the serum levels of IL‐10 and IL‐12, as well as T‐cell stimulation assays in peripheral blood to address immune response in individuals with PROGINS. Results: We found a significant association between the presence of PROGINS mutation and HEV seroprevalence in individuals infected with HIV (30% in HIV+/HEV+ versus 2% in HIV+/HEV, respectively, P = .009). Moreover, we found that HIV+/HEV+ individuals expressing the PROGINS mutation had lower serum levels of IL‐10 and higher levels of IL‐12. The presence of the mutation led to a reduced response upon stimulation of CD4+ and CD8+ T cells compared to those without the mutation, suggesting an immune modulation associated with PROGINS. Conclusions: Our study identified a mutation in the PR that provides significant insights into mechanisms of HEV infection in immunosuppressed individuals. [ABSTRACT FROM AUTHOR]

Background & Aims: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. Most studies addressing the epidemiology of HCC originate from developed countries. This study reports the preliminary findings of a multinational approach to characterize HCC in South America. Methods: We evaluated 1336 HCC patients seen at 14 centres in six South American countries using a retrospective study design with participating centres completing a template chart of patient characteristics. The diagnosis of HCC was made radiographically or histologically for all cases according to institutional standards. Methodology of surveillance for each centre was following AASLD or EASL recommendations. Results: Sixty-eight percent of individuals were male with a median age of 64 years at time of diagnosis. The most common risk factor for HCC was hepatitis C infection (HCV, 48%), followed by alcoholic cirrhosis (22%), Hepatitis B infection (HBV, 14%) and NAFLD (9%). We found that among individuals with HBV-related HCC, 38% were diagnosed before age 50. The most commonly provided therapy was transarterial chemoembolization (35% of HCCs) with few individuals being considered for liver transplant (<20%). Only 47% of HCCs were diagnosed during surveillance, and there was no difference in age of diagnosis between those diagnosed incidentally vs by surveillance. Nonetheless, being diagnosed during surveillance was associated with improved overall survival (P = .01). Conclusions: Our study represents the largest cohort to date reporting characteristics and outcomes of HCC across South America. We found an important number of HCCs diagnosed outside of surveillance programmes, with associated increased mortality in those patients. [ABSTRACT FROM AUTHOR]

Background: Infection with the hepatitis E virus (HEV) can cause acute hepatitis in endemic areas in immunecompetent 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 < 0.001 and OR: 3.7, 95% CI 2.35-5.92, p < 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

The article offers information about the epidemiology of hepatocellular carcinoma (HCC) in South America, based on a multicenter study across six countries, and highlights the impact of non-alcoholic fatty liver disease (NAFLD) as a rising risk factor for HCC. It discusses the potential biases of single-center studies and the impact of the COVID-19 pandemic on healthcare access and utilization.

Simple Summary: Non-homeostatic cytokine expression during hepatocellular carcinogenesis, together with simple and inexpensive cytokine detection techniques, has opened up its use as potential biomarkers, from cancer detection to prognosis. However, carcinogenic programs during cancer progression are not linear. Therefore, cytokines with prognostic potential in one stage may not be relevant in another. Here, we reviewed cytokines with clinical potential in different settings during hepatocellular carcinoma progression. Hepatocellular carcinoma (HCC) is the primary form of liver cancer and a leading cause of cancer-related death worldwide. Early detection remains the most effective strategy in HCC management. However, the spectrum of underlying liver diseases preceding HCC, its genetic complexity, and the lack of symptomatology in early stages challenge early detection. Regardless of underlying etiology, unresolved chronic inflammation is a common denominator in HCC. Hence, many inflammatory molecules, including cytokines, have been investigated as potential biomarkers to predict different stages of HCC. Soluble cytokines carry cell-signaling functions and are easy to detect in the bloodstream. However, its biomarkers' role remains limited due to the dysregulation of immune parameters related to the primary liver process and their ability to differentiate carcinogenesis from the underlying disease. In this review, we discuss and provide insight on cytokines with clinical relevance for HCC differentiating those implicated in tumor formation, early detection, advanced disease, and response to therapy. [ABSTRACT FROM AUTHOR]

Background Treatment of HCV with direct-acting antivirals has enabled the discussion of HCV eradication worldwide. Envisioning this aim requires implementation of mass screening in resource-limited areas, usually constrained by testing costs. Methods We validated a low-cost, rapid diagnosis test (RDT) for HCV in three different continents in 141 individuals. Results The HCV RDT showed 100% specificity and sensitivity across different samples regardless of genotype or viral load (in samples with such information, 90%). Conclusions The HCV test validated in this study can allow for HCV screening in areas of need when properly used. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented about a prospective cohort study which determined the incidence of hepatitis B (HBV) coinfection in HIV-infected persons in Tanzania.