Current status of etiology and outcomes of acute liver failure in India-A multicentre study from tertiary centres.

BACKGROUND AND AIMS: Acute liver failure (ALF) is a medical emergency and liver transplantation (LT) may be required as definitive therapy. The etiology varies across geographical locations and is mostly viral dominant in India. We aimed at evaluating the spectrum, impact of interventions (plasma exchange [PLEx], continuous renal replacement therapy [CRRT]) and outcomes of ALF in India in recent times. METHODS: A multicentre retrospective study across four major tertiary care centres. RESULTS: As many as 183 ALF patients (median age, 23 years; females, 43.1%; model for end-stage liver disease [MELD], 32.7) from January 2021 to December 2023 were included. Nineteen per cent had infection and 40.4% of patients satisfied King's College criteria (KCC) at admission. Most common cause for ALF was hepatitis A virus (HAV) (44.2%) followed by rodenticide poisoning (10.3%). Approximately 35% of patients each received either PLEx or CRRT. The 7, 14 and 21-day transplant-free survival probability was 65.5%, 60.1%, and 57.3%, respectively. Only 3.8% of patients underwent liver transplantation. On multivariable Cox regression analysis, hemoglobin (HR, 0.74 [0.63-0.87]), lactate (HR, 1.14 [1.03-1.26]), advanced hepatic encephalopathy (HE) (HR, 4.87 [1.89-12.5]) and fulfilling KCC [HR, 10.04 [4.57-22.06]) at admission were the independent predictors of mortality. A model including KCC + lactate + HE ≥ 3 with or without hemoglobin had an AUROC of 0.81-0.84 to predict mortality. In those who underwent PLEx, advanced HE (HR, 4.13 [1.75-9.7]), procalcitonin (HR, 1.18 [1.07-1.30]) and KCC (HR, 4.6 [1.6-13.1), while for those who received CRRT, lactate (HR, 1.37 [1.22-1.54]) and KCC (HR, 6.4 [2.5-15.8]) independently predicted mortality. CONCLUSIONS: Hepatitis A virus is currently the most common cause for ALF in India, emphasizing the need for universal vaccination programmes. Spontaneous survival in tertiary care centres is 57%. LT rates were low.

A Rare Presentation of Glucose-6-Phosphate Dehydrogenase Deficiency.

Approximately 400 million individuals globally experience glucose-6-phosphate dehydrogenase (G6PD) insufficiency, an enzymatic condition that may be hazardous. Because of mutations in the G6PD gene, which result in functional variants alongside a variety of biochemical and clinical symptoms, this condition is an X-linked hereditary genetic disorder. Our case is that of a 12-year-old male child who presented with acute liver failure and later on, exhibited signs of hemolysis as well. We had to rule out the possibilities of acetaminophen toxicity and hepatitis A before reaching the conclusion that an underlying G6PD deficiency was being exacerbated by viral infection and simultaneous ingestion of non-steroidal anti-inflammatory drugs (NSAIDs).

Healthcare resource utilization and costs associated with hepatitis A in the United States: a retrospective database analysis.

AIM: To investigate hepatitis A-related healthcare resource use and costs in the US. METHODS: The Merative Marketscan Commercial Claims and Encounters database was retrospectively analyzed for hepatitis A-related inpatient, outpatient, and emergency department (ED) claims from January 1, 2012 to December 31, 2018. We calculated the hepatitis A incidence proportion per 100,000 enrollees, healthcare resource utilization, and costs (in 2020 USD). Results were stratified by age, gender, and select comorbidities. RESULTS: The overall hepatitis A incidence proportion was 6.1 per 100,000 enrollees. Among individuals with ≥1 hepatitis A-related claim, the majority (92.6%) had ≥1 outpatient visit related to hepatitis A; 9.1% were hospitalized and 4.2% had ≥1 ED visit. The mean (standard deviation [SD]) length of hospital stay was 5.2 (8.1) days; the mean (SD) number of outpatient and ED visits were 1.3 (1.3) and 1.1 (0.6), respectively. The incidence proportion per 100,000 was higher among adults than children (7.5 vs. 1.5), individuals with HIV than those without (126.7 vs. 5.9), and individuals with chronic liver disease than those without (143.6 vs. 3.8). The total mean (SD)/median (interquartile range, IQR) per-patient cost for hepatitis A-related care was $2,520 ($10,899)/$156 ($74-$529) and the mean cost of hospitalization was 18.7 times higher than that of outpatient care ($17,373 vs. $928). LIMITATIONS: The study data included only a commercially insured population and may not be representative of all individuals. CONCLUSIONS: In conclusion, hepatitis A is associated with a substantial economic burden among privately insured individuals in the US.

Hepatitis A is an acute liver infection caused by the hepatitis A virus. In the US, safe and effective vaccines for hepatitis A have been available since 1996. Vaccination recommendations include children (all children aged 12­23 months and previously unvaccinated children aged 2­18 years old) and adults at risk of infection or severe disease (e.g. international travelers, men who have sex with men, persons experiencing homelessness, persons with chronic liver disease or persons with HIV infection). Since 2016, the US has experienced person-to-person outbreaks of hepatitis A, primarily affecting unvaccinated individuals who use drugs or are experiencing homelessness. To better understand the impact of hepatitis A in the US, we assessed healthcare resource use and costs in 15,435 patients with hepatitis A from 2012 to 2018 in the Merative Marketscan Commercial Claims and Encounters database. We found that slightly more than 6 per 100,000 enrollees had hepatitis A from 2012 to 2018 and the number of people treated for hepatitis A per 100,000 was highest for people living with HIV or with chronic liver disease. The majority (92.6%) of people reported at least an outpatient visit, 9.1% were hospitalized, and 4.2% had an emergency department visit. The average cost for hepatitis A-related care was $2,520 per patient and was 18.7 times higher for hospitalized patients ($17,373) than for patients treated in outpatient care ($928). Our results are limited by the generalizability of the dataset, which is a convenience sample of private insurance claims, and are therefore unlikely to capture groups at high-risk for hepatitis A, such as individuals experiencing homelessness. In conclusion, hepatitis A leads to considerable healthcare costs for privately insured individuals in the US.

Development of the first officially licensed live attenuated duck hepatitis A virus type 3 vaccine strain HB80 in China and its protective efficacy against DHAV-3 infection in ducks.

Duck hepatitis A virus type 3 (DHAV-3) is an infectious virus that is highly fatal to ducklings and causes significant economic losses in the duck industry worldwide. Biosecurity and vaccination are required to control the pathogen. In the present study, we attenuated a lowly pathogenic DHAV-3 clinical isolate, named as HB, by serial passaging in duck embryos, and followed by several adaptive proliferations in specific-pathogen-free (SPF) chicken embryos. The virulence of DHAV-3 at different passages was assessed by infecting 3-day-old ducklings. We found that the HB strain lost pathogenicity to ducklings from the 55th passage onwards. The 80th passage strain (HB80), which achieved good growth capacity in duck embryos with a viral titer of 108.17 50% egg lethal dose per milliliter (ELD50/mL), was selected as a live attenuated vaccine candidate. The HB80 strain did not induce clinical symptoms or pathological lesions in 3-day-old ducklings and showed no virulence reversion after 5 rounds of in vivo back-passage. The minimum effective dose of HB80 was determined to be 104.5 ELD50 by hypodermic inoculation of the neck. Importantly, a single dose of HB80 elicited good immune responses and provided complete protection against challenge with the lethal DHAV-3 strain. Compared with the genomic sequence of the parental HB strain, HB80 had 7 amino acid substitutions, two of them are in the hypervariable region of the VP1 and polymerase-encoding 3D regions, which may play a role in virulence attenuation. Our data suggest that the attenuated HB80 strain is a promising vaccine candidate for the prevention of DHAV-3 infections in China. HB80 has been registered as a New Veterinary Drug Registration Certificate by the Chinese Ministry of Agriculture and Rural Affairs (MARA), and is the first live attenuated DHAV-3 vaccine strain to be officially licensed in China.

Safety and 6-month immune persistence of inactivated poliovirus vaccine (Sabin strains) simultaneously administrated with other vaccines for primary and booster immunization in Jiangxi Province, China.

OBJECTIVES: This study aims to evaluate the safety of a new inactivated poliomyelitis vaccine (Sabin strains) (sIPV) for large-scale use in primary and booster immunizations, whether simultaneously administered with other vaccines or not and to explore the persistence of all vaccines at approximately six months after vaccination. METHOD: A total of 3200 infants were recruited into this study, including 2000 infants aged 2-3 months randomly assigned (1:1) into the "sIPV basic" or the "sIPV+DTaP" group for primary immunization of sIPV. Another 1200 children aged 18 months old and above were randomly assigned (2:2:1:1) into the "sIPV booster," "sIPV+HepA-I," "sIPV+MMR", or "sIPV+HepA-L" group for booster immunization of sIPV. Adverse events within 30 days of each vaccination dose in all participants were self-reported by guardians using a WeChat mini-program. Approximately 200 blood samples were collected at 5-7 months after the final vaccination to test for antibodies against poliovirus and other viruses. RESULTS: 3198 participants in total were included in the safety study, including 1999 infants aged 2-3 months old and 1199 children aged 18-26 months old. For primary immunization, the incidence of adverse reactions in the "sIPV basic" and the "sIPV+DTaP" group were 3.19 and 6.21% (P = 0.001), respectively. For booster immunization, the incidences of adverse reaction for the "sIPV booster" group were 2.25%, while the incidence for the "sIPV +others" group in total was 2.50% (P = 0.788). Most adverse reactions were mild. Fever was the most common symptom in all groups. No vaccine-related serious adverse events (SAEs) were observed in this study. The seropositivity rates of antibodies in the "sIPV basic" and the "sIPV+DTaP" group were 92.31 and 100% against type 1 poliovirus (P = 0.031); 96.15% and 98.57% against type 2 poliovirus (P = 0.575); 98.08% and 91.43% against type 3 poliovirus (P = 0.237), respectively. Regarding booster vaccination with sIPV, whether co-administered with other vaccines or not, the seropositivity rates of antibodies against the three types of polioviruses were all 100%. Seropositivity rates of antibodies against hepatitis A, measles, mumps, and rubella were all no <77%, except for pertussis, which was <30%. CONCLUSION: sIPV demonstrated good safety and immune persistence for primary and booster vaccinations, whether administered singly or simultaneously. Antibodies against hepatitis A, measles, mumps and rubella were not disrupted by the co-vaccination. However, the seropositivity rates and geometric mean concentrations (GMCs) of antibodies against pertussis indicate the necessity for a booster dose.

Comparison of Anti-Hepatitis A Antibody Pharmacokinetics in Healthy Australian Subjects Receiving Standard or Weight-Based Dosing of Polyvalent Immunoglobulin.

This randomized controlled trial compared two dosing regimens of the polyvalent immunoglobulin available for hepatitis A post-exposure prophylaxis in Australia. Participants were randomized to receive either 270 IU (standard dose) or 3.375 IU/kg (dose by weight). Quantitative serial serum hepatitis A antibody concentrations were measured at baseline and then on days 1, 3, 7, 28, and 50. Fifteen participants completed the trial. Serum hepatitis A antibody concentrations were not different between the study groups at any time point. Pharmacokinetic parameters estimated from participant data were not different between the study groups. The hepatitis A antibody level of all participants exceeded 10 mIU/mL at day 50. While no difference between dosing regimens was found in this study, further research should examine dosing at the lower limit of current Australian recommendations before making policy decisions.

Hepatitis A in Latin America: The current scenario.

This review aims to gather and disseminate updated information regarding hepatitis A virus (HAV) in Latin America (LA) in the last 11 years, including seroprevalence, post-vaccination studies, virus detection in aqueous matrices and food samples, and outbreak reports. Only 24 seroprevalence studies were published between 2012 and 2023 with 55%-100% reported prevalences of anti-HAV IgG. Among the 25 LA countries, only eight of them have introduced HAV vaccines into their immunisation programs. Outbreaks of hepatitis A occurred between 2017-2019, mainly affecting men who have sex with men in Argentina, Brazil and Chile, probably as a consequence of the abrupt decline of young adults' immunity. This could be due to that young adult have never been infected in childhood (due to socio-health improvements) and are above the cut-off ages to be included when the vaccination programs were introduced. Although scarce, studies focused on environmental and food HAV surveillance have shown viral presence in these samples. Surface waters presented HAV detections between 1.2% and 86.7%, and untreated wastewaters between 2.8% and 70.9%. Genotypes found in all cases were IA and IC. The only wastewater-based epidemiology study showed to be a useful tool as a complement of traditional epidemiological surveillance. Only four LA countries have looked for HAV in food samples, with genome detection rates between 9% and 33%. Latin American HAV circulation scenario is changing. In countries where socioeconomic and sanitary conditions have not improved, the virus persists with high endemicity and the access to the vaccine should be re-evaluated by local governments. In countries where access to clean water, better sanitary conditions and HAV immunisation programs have been implemented, the number of cases among young adults seems to be increasing, alerting health authorities.

Concurrently Affected by Dengue and Hepatitis A: Exploring the Intricacies of Co-infection in a Comprehensive Case Series.

Based on the examination of four distinct cases, this case series offers a thorough investigation of the intricate relationship between dengue fever and hepatitis A infection. Despite their distinct origins, both illnesses manifest overlapping clinical features, posing considerable diagnostic hurdles, particularly in endemic regions. The cases reveal consistent symptoms such as elevated fever, abdominal discomfort, jaundice, and irregular liver function test results, underscoring the intricate nature of an accurate diagnosis. Variations in age distribution and the severity of symptoms underscore the necessity for tailored treatment approaches. Diagnostic challenges stem from the similarity in clinical presentations and shared laboratory abnormalities, necessitating comprehensive serological assessments. Therapeutic strategies entail a multidisciplinary approach addressing both hepatic and systemic manifestations, with supportive measures ensuring favorable clinical outcomes. Despite the complexities involved, timely interventions facilitate gradual symptom amelioration and successful patient recovery. Informing clinical practice and directing public health actions, this case series provides insightful information about the diagnostic and treatment complications associated with co-occurring dengue fever and hepatitis A infection.

Modeling hepatitis A epidemiological profiles and estimating the pediatric vaccination threshold in the Russian Federation.

Background: To combat the hesitancy towards implementing a hepatitis A universal mass vaccination (UMV) strategy and to provide healthcare authorities with a comprehensive analysis of the potential outcomes and benefits of the implementation of such a vaccination program, we projected HAV seroprevalence and incidence rates in the total population of the Russian Federation and estimated the pediatric vaccination threshold required to achieve an incidence level of less than 1 case per 100,000 using a new mathematical model. Methods: A dynamic age-structured SEIRV (susceptible-exposed-infectious-recovered-vaccinated) compartmental model was developed and calibrated using demographic, seroprevalence, vaccination, and epidemiological data from different regions of the Russian Federation. This model was used to project various epidemiological measures. Results: The projected national average age at the midpoint of population immunity increases from 40 years old in 2020 to 50 years old in 2036 and is shifted even further to the age of 70 years in some regions of the country. An increase of varying magnitude in the incidence of symptomatic HAV infections is predicted for all study regions and for the Russian Federation as a whole between 2028 and 2032, if the HAV vaccination coverage level remains at the level of 2022. The national average vaccination coverage level required to achieve a symptomatic HAV incidence rate below 1 case per 100,000 by 2032 was calculated to be 69.8% if children aged 1-6 years are vaccinated following the implementation of a UMV program or 34.8% if immunization is expanded to children aged 1-17 years. Conclusion: The developed model provides insights into a further decline of herd immunity to HAV against the background of ongoing viral transmission. The current favorable situation regarding hepatitis A morbidity is projected to be replaced by an increase in incidence rates if vaccination coverage remains at the current levels. The obtained results support the introduction of a hepatitis A UMV strategy in the Russian Federation.

Surface Display of Duck Hepatitis A Virus Type 1 VP1 Protein on Bacillus subtilis Spores Elicits Specific Systemic and Mucosal Immune Responses on Mice.

Duck viral hepatitis, primarily caused by duck hepatitis A virus type 1 (DHAV-1), poses a significant threat to the global duck industry. Bacillus subtilis is commonly utilized as a safe probiotic in the development of mucosal vaccines. In this study, a recombinant strain of B. subtilis, designated as B. subtilis RV, was constructed to display the DHAV-1 capsid protein VP1 on its spore surface using the outer coat protein B as an anchoring agent. The immunogenicity of this recombinant strain was evaluated in a mouse model through mixed feeding immunization. The results indicated that B. subtilis RV could elicit specific systemic and mucosal immune responses in mice, as evidenced by the high levels of serum IgG, intestinal secretory IgA, and potent virus-neutralizing antibodies produced. Furthermore, the recombinant strain significantly upregulated the expression levels of IL-2, IL-6, IL-10, TNF-α, and IFN-γ in the intestinal mucosa. Thus, the recombinant strain maintained the balance of the Th1/Th2 immune response and demonstrated an excellent mucosal immune adjuvant function. In summary, this study suggests that B. subtilis RV can be a novel alternative for effectively controlling DHAV-1 infection as a vaccine-based feed additive.

Effectiveness of a Counseling Intervention to Increase Vaccination Uptake among Men Who Have Sex with Men during the Mpox Outbreak.

Men who have sex with men (MSM) are disproportionately impacted by sexually transmitted infections (STIs), including HIV and those preventable through vaccination such as mpox, HPV, HAV, and HBV. A retrospective cohort study was conducted to evaluate the effectiveness of counseling provided during mpox vaccination on the uptake of other recommended vaccines (HPV, HAV, and HBV) and to identify associated factors. Relevant covariates such as nationality, age, HIV status, and use of PrEP were retrieved from electronic medical records. Vaccination status data were retrieved from the regional vaccination registry. Of the 330 participants, 98.8% were males and the mean age was 40.6 years (SD: 11.2). Following consultation, a statistically significant increase for both HPV (from 25.8% to 39.1%) and HAV (from 26.7% to 36.1%) was observed (p < 0.001). The multivariate analysis showed a significant negative association between the uptake of HPV and HBV vaccines and foreign nationality (aOR 0.25 (95%CI 0.08-0.69), p = 0.012; and aOR 0.31 (95%CI 0.11-0.81), p = 0.021). The HBV vaccine uptake was negatively associated with increasing age. Our results suggest that tailored counseling can effectively bridge the gap in vaccine acceptance among vulnerable populations, thereby improving overall public health outcomes.

Factors Associated With Hepatitis A Seropositivity at 23 Years After Childhood Vaccination.

We evaluated factors associated with the presence of hepatitis A virus antibodies 23 years after initiating vaccination at ages 6-15 months. Among 67 participants, 86% (42/49) of those vaccinated at ages 12-15 months and 61% (11/18) of those vaccinated at 6 months remained seropositive at 23 years. Lack of maternal antibodies at enrollment and higher initial vaccine response were independently associated with higher antibody concentrations at 23 years. Further research is needed to assess the duration of hepatitis A vaccine protection and possible need for a booster dose.

Reconstruction of the historic time course of blood-borne virus contamination of clotting factor concentrates, 1974-1992.

Factor VIII and IX clotting factor concentrates manufactured from pooled plasma have been identified as potent sources of virus infection in persons with hemophilia (PWHs) in the 1970s and 1980s. To investigate the range and diversity of viruses over this period, we analysed 24 clotting factor concentrates for several blood-borne viruses. Nucleic acid was extracted from 14 commercially produced clotting factors and 10 from nonremunerated donors, preserved in lyophilized form (expiry dates: 1974-1992). Clotting factors were tested by commercial and in-house quantitative PCRs for blood-borne viruses hepatitis A, B, C and E viruses (HAV, HBV, HCV, HEV), HIV- types 1/2, parvoviruses B19V and PARV4, and human pegiviruses types 1 and 2 (HPgV-1,-2). HCV and HPgV-1 were the most frequently detected viruses (both 14/24 tested) primarily in commercial clotting factors, with frequently extremely high viral loads in the late 1970s-1985 and a diverse range of HCV genotypes. Detection frequencies sharply declined following introduction of virus inactivation. HIV-1, HBV, and HAV were less frequently detected (3/24, 1/24, and 1/24 respectively); none were positive for HEV. Contrastingly, B19V and PARV4 were detected throughout the study period, even after introduction of dry heat treatment, consistent with ongoing documented transmission to PWHs into the early 1990s. While hemophilia treatment is now largely based on recombinant factor VIII/IX in the UK and elsewhere, the comprehensive screen of historical plasma-derived clotting factors reveals extensive exposure of PWHs to blood-borne viruses throughout 1970s-early 1990s, and the epidemiological and manufacturing parameters that influenced clotting factor contamination.

Prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency among the fulminant hepatitis A virus infection patients.

Background: Hepatitis A is a widespread viral infection with significant public health implications. Assessing glucose 6-phosphate dehydrogenase (G6PD) deficiency in hepatitis A patients is essential for various reasons, including prognosis, disease severity evaluation, encephalopathy risk identification, tailored management, and advancing scientific understanding. This study aimed to investigate the prevalence and clinical implications of G6PD impairment in individuals with fulminant hepatitis A. Methods: A cross-sectional descriptive analysis was conducted, involving hospitalized patients with fulminant hepatitis A. Demographic data, prevalence rates, and clinical findings were recorded in a database. The diagnosis of hepatitis A infection was confirmed using an anti-HAV IgM antibody test, and G6PD enzyme activity was measured with a fluorescent spot assay. Results: Out of 81 patients with hepatitis A, 57 (70.4%) were males, and 24 (29.5%) were females, with an average age of 24.6 years. Dark yellow urine and anorexia were the most common clinical symptoms. Notably, 30 (37%) patients lacked G6PD. The group with G6PD deficiency showed significantly higher rates of encephalopathy and mortality (P<0.01), along with elevated bilirubin (P=0.00), abnormal coagulation parameters, and low hemoglobin levels (P=0.00). Conclusion: In light of these findings, the present study proposes the implementation of routine G6PD level assessments and the evaluation of other relevant markers in regions where hepatitis A is endemic. Furthermore, the study underscores the need for vigilant monitoring of hemolysis and encephalopathy in affected patients to optimize clinical management and reduce morbidity and mortality associated with this condition.

Designing the fusion protein of rotavirus VP8 and hepatitis A virus VP1 and evaluating the immunological response in BALB/c mice.

Background and Objectives: Rotavirus and Hepatitis A virus are responsible for causing gastroenteritis and jaundice. The current vaccination approaches have proven insufficient, especially in low-income countries. In this study, we presented a novel dual-vaccine candidate that combines the rotavirus VP8 protein and the hepatitis A virus VP1. Materials and Methods: The VP8*-rotavirus+AAY+HAV-VP1 fusion protein was produced using an Escherichia coli expression system. The recombinant protein had a molecular weight of approximately 45.5 kDa and was purified through affinity chromatography. BALB/c mice were injected subcutaneously with the recombinant protein, VP1, VP8 and vaccines for rotavirus and hepatitis A virus, both with and without ALUM and M720 adjuvants. ELISA assays were used to measure total IgG, IgG1, IgG2, and short-term and long-term IL-5 and IFN-γ responses. Results: The fusion protein, when combined with adjuvants, elicited significantly higher total IgG, IgG1, and IgG2 responses compared to VP1 and VP8 alone, as well as the rotavirus and hepatitis A vaccines. Furthermore, it induced a higher short-term IL-5 and IFN-γ response while demonstrating a higher long-term IL-5 response compared to the rotavirus and hepatitis A vaccines. Conclusion: This study demonstrates that the VP8*-rotavirus+AAY+HAV-VP1 fusion protein is a promising dual vaccine candidate for immunization against hepatitis A and rotaviruses.

Therapeutic plasma exchange provides native liver survival benefit in children with acute liver failure: A propensity score-matched analysis.

OBJECTIVES: This study aimed to evaluate the safety and efficacy of therapeutic plasma exchange (TPE) in pediatric acute liver failure (PALF). METHODS: All children aged 2-18 years with PALF were included. The intervention cohort included a subset of PALF patients undergoing complete three sessions of TPE, whereas the matching controls were derived by propensity score matching from the patient cohort who did not receive any TPE. Propensity matching was performed based on the international normalized ratio (INR), grade of hepatic encephalopathy (HE), age, bilirubin, and ammonia levels. The primary outcome measure was native liver survival (NLS) in the two arms on day 28. RESULTS: Of the total cohort of 403 patients with PALF, 65 patients who received TPE and 65 propensity-matched controls were included in analysis. The 2 groups were well balanced with comparable baseline parameters. On day 4, patients in the TPE group had significantly lower INR (P = 0.001), lower bilirubin (P = 0.008), and higher mean arterial pressure (MAP) (P = 0.033) than controls. The NLS was 46.15% in the TPE arm and 26.15% in the control arm. The overall survival (OS) was 50.8% in the TPE arm and 35.4% in the control arm. Kaplan-Meier survival analysis showed a significantly higher NLS in patients receiving TPE than controls (P = 0.001). On subgroup analysis, NLS benefit was predominantly seen in hepatitis A-related and indeterminate PALF. CONCLUSION: TPE improved NLS and OS in a propensity-matched cohort of patients with PALF. Patients receiving TPE had lower INR and bilirubin levels and higher MAP on day 4.

Indicator and pathogenic virus removal in bench scale soil aquifer treatment.

The demonstration of enteric virus removal for indirect potable reuse of advanced purified water is necessary to ensure safe water reclamation practices. This study evaluated the efficacy of soil treatment in reducing concentrations of Pepper Mild Mottle Virus (PMMoV), Hepatitis A (HAV), and Norovirus (NoV) gene markers through bench scale unsaturated soil columns. Three different infiltration rates were evaluated to determine their impact on viral gene marker removal. The concentrations of viral markers in the column influent and effluent samples were measured through RNA extraction and then RT-qPCR, and the log reduction values (LRVs) were calculated to quantify the effectiveness of removal across the columns. The LRVs achieved for PMMoV were 2.80 ± 0.36, 2.91 ± 0.48, and 2.72 ± 0.32 for infiltration rates of 4.9 mm/h, 9.4 mm/h, and 14.0 mm/h, respectively. A one-way ANOVA indicated no statistically significant differences in LRVs among the various infiltration rates (p-value = 0.329). All samples measured for HAV were below the detection limit both in the influent and effluent of the soil columns. While NoV GI and GII markers were measurable in the soil column influent, they were removed to below the detection limit in the effluent. The use of half the Limit-of-Detection (LoD) for effluent values enabled the estimation of log removals, which were calculated as 1.42 ± 0.07, 1.64 ± 0.29, and 1.74 ± 0.18 for NoV GI and 1.14 ± 0.19, 1.58 ± 0.21, and 1.87 ± 0.41 for NoV GII at infiltration rates of 4.9 mm/h, 9.4 mm/h, and 14.0 mm/h. This highlights the efficacy of soil treatment in reducing virus gene marker concentrations at various infiltration rates, and that spreading basins employed for reclaimed water recharge to ground water aquifers are an effective method for reducing the presence of viral contaminants in indirect potable reuse systems.

Healthcare and Epidemiological Surveillance Costs of Hepatitis A Outbreaks in Spain in Regions with and without Universal Hepatitis A Vaccination of Children during 2010-2018.

The aim of this study was to evaluate and compare hepatitis A outbreak-associated healthcare and epidemiological surveillance costs in Spain in two types of autonomous regions during 2010-2018: (1) regions with a prevention strategy based on universal hepatitis A vaccination of children and vaccination of high-risk population groups (Catalonia) and (2) regions with a prevention strategy based on vaccinating high-risk population groups (Castile and Leon, Murcia, Navarra, Community of Madrid, Community of Valencia). Healthcare costs were determined based on the resources used to treat hepatitis A outbreak-associated cases and hospitalizations. Epidemiological surveillance costs were calculated from the resources used during surveillance activities. The ratios for total, healthcare and epidemiological surveillance costs (regions without universal hepatitis A vaccination of children vs. Catalonia) were used to compare the two hepatitis A prevention strategies. From 2010 to 2018, the total, healthcare and epidemiological surveillance costs per million population were 1.75 times (EUR 101,671 vs. EUR 58,032), 1.96 times (EUR 75,500 vs. EUR 38,516) and 1.34 times greater (EUR 26,171 vs. EUR 19,515) in regions without universal hepatitis A vaccination of children than in Catalonia, respectively. The ratios tended to increase over time during 2010-2018. In 2015-2018, total, healthcare and epidemiological surveillance costs per million population were 2.68 times (EUR 69,993 vs. EUR 26,158), 2.86 times (EUR 53,807 vs. EUR 18,825) and 2.21 times greater (EUR 16,186 vs. EUR 7333) in regions without universal hepatitis A vaccination of children than in Catalonia, respectively. These findings suggest that universal hepatitis A vaccination of children could reduce hepatitis A outbreak-associated costs.

Antibody persistence 7 years after hepatitis-A vaccine in children with human immunodeficiency virus infection.

BACKGROUND: HIV-infected children have a higher risk of presenting infections, including the hepatitis A virus (HAV). The inactivated HAV vaccine is immunogenic in immunocompetent hosts; however, there are insufficient studies on the duration of seroprotection in HIV-infected children. METHODS: An analytical cohort study was conducted. HIV-1-infected children who received the inactivated HAV vaccine (2 doses) were included. Blood samples were taken for antibody measurement, the first one 28 days after the second dose and another 7 years after the vaccination schedule. Information on viral load, immunological category, weight, height, and response to antiretroviral treatment from diagnosis to the last assessment was obtained. RESULTS: 19 patients were included, with a mean age of 12.6 years (SD ± 2.29). 58% were male. 80% of the patients presented protective immunoglobulin G antibodies against HAV 7-year post-vaccination. The antibody concentration was found to be between 13 and 80 mIU/mL (median of 80 mIU/mL). 52% showed some degree of immunosuppression. There was no statistically significant relationship between the presence of seroprotection and viral load, treatment failure, immunological category, and malnutrition. Twelve patients presented with antiretroviral treatment failure, and in 33% of them, the antibodies did not offer satisfactory seroprotection. CONCLUSION: 7-year post-vaccination, 80% of HIV-infected children maintain seroprotection titers against HAV.

INTRODUCCIÓN: Los niños infectados por el virus de la inmunodeficiencia humana (VIH) tienen mayor riesgo de presentar infecciones, incluyendo hepatitis por virus A (VHA). La vacuna inactivada contra el VHA es inmunógena en el huésped inmunocompetente. No hay estudios suficientes sobre el tiempo de seroprotección en niños infectados por el VIH. MÉTODO: Estudio de cohorte, analítico. Se incluyeron niños con infección por VIH-1 que recibieron la vacuna inactivada contra el VHA (dos dosis). Se les tomaron muestras sanguíneas para medición de anticuerpos, una 28 días después de la segunda dosis y otra 7 años después del esquema de vacunación. Se obtuvo información de carga viral, categoría inmunológica, peso y talla, y respuesta al tratamiento antirretroviral desde el diagnóstico hasta la última valoración. RESULTADOS: Se incluyeron 19 pacientes con una edad media de 12.6 años (± 2.29). El 58% fueron del sexo masculino. El 80% de los pacientes presentaron anticuerpos immunoglobulin G (IgG) contra el VHA protectores a los 7 años de la vacunación. La concentración de anticuerpos se encontró entre 13 y 80 mUI/ml (mediana: 80 mUI/ml). El 52% mostraron algún grado de inmunosupresión. No existe relación estadísticamente significativa entre la presencia de seroprotección y la carga viral, la falla al tratamiento, la categoría inmunológica ni la desnutrición. Doce pacientes presentaron falla al tratamiento antirretroviral; en el 33% de ellos los anticuerpos no ofrecían seroprotección satisfactoria. CONCLUSIONES: A 7 años posvacunación, el 80% de los niños con VIH mantienen títulos de seroprotección frente al VHA.

Hepatitis A virus infection associated with bilateral pleural effusion, ascites, and acalculous cholecystitis in childhood: a case report.

BACKGROUND: Acute hepatitis A infection is common among children in developing nations. The clinical presentation in children is usually asymptomatic and anicteric, and it is a self-limiting infection. Rarely, it can be associated with extrahepatic complications such as pleural effusion, acalculous cholecystitis, and ascites. CASE PRESENTATION: An 8-year-old middle eastern child presented with abdominal pain, jaundice in the sclera, yellowish color of urine, and poor appetite. In the last two days, abdominal distension developed. After conducting diagnostic investigations, the child was diagnosed with HAV hepatitis associated with bilateral pleural effusion, acalculous cholecystitis, and ascites. He was managed conservatively with vitamin K supplementation and supportive parenteral fluids. After 4 days, clinical improvement was observed. CONCLUSION: Hepatitis A infections presented with extrahepatic manifestations like pleural effusion, acalculous cholecystitis, and ascites are very rare, especially in children. There have been some reports of these manifestations occurring in isolation, but for them to co-exist to our knowledge, this has only been reported in two cases in the literature, and this is the third case with all these three rare complications being presented simultaneously in a single child. Although HAV infection is an asymptomatic and self-limiting viral disease in childhood, it can manifest with rare extrahepatic complications, so pediatricians should be aware of this rare association to avoid unnecessary investigations.