Association of climate variability with hepatitis A and E infections in Dhaka (2016–2023)

Etiologies and Features of Acute Viral Hepatitis in Spain

For decades, hepatitis A virus (HAV) has been a leading cause of acute hepatitis among children and was less prevalent among adults. However, recently a paradigm shift has been observed in the epidemiology of HAV, as evident by cases of acute hepatitis due to HAV among adults. To estimate frequency of HAV in acute viral hepatitis and compare characteristics in HAV and hepatitis E virus (HEV) infection. This was a trend analysis conducted at Aga Khan University Hospital Karachi (Sindh, Pakistan) from February 2024 to May 2024. Individuals aged 18 years and older diagnosed with acute viral hepatitis attributed to hepatotropic viruses in 2024 were reviewed. To compare the trend patients admitted with acute hepatitis during 2019-2023 were also reviewed. Data regarding clinical and laboratory parameters were recorded. The yearly trend of acute hepatitis due to HAV and HEV was analyzed, and comparative analysis was done between HAV and HEV cases among adults. A total of 396 patients were found to have acute hepatitis during our study duration. HAV was diagnosed in 234 patients (59%) while 157 patients (39.6%) were found to have acute HEV infection. Additionally, acute hepatitis B virus infection was identified in 3 patients (0.7%), whereas acute hepatitis C virus infection was found in 2 (0.5%) cases of acute hepatitis. Yearly trends showed increasing occurrence of HAV infection among adults over last 5 years. The patients with acute HAV were younger than patients with HEV (28 years ± 8 years vs 30 years ± 8 years; P < 0.01). Higher levels of total bilirubin were seen in HEV infection, while higher levels of alanine transaminase were seen in HAV infection. However, a higher proportion of acute liver failure (ALF), coagulopathy, and mortality were observed in HEV. An increase in acute hepatitis A cases among adults shows less severity than hepatitis E, highlighting the need for better sanitation, hygiene, and adult hepatitis A vaccination programs.

The acute viral hepatitis was one of the most common conditions in daily clinical practice varying in different parts of the world. The aim of the present study was to perform a comparative analysis on clinical characteristics among patients with acute hepatitis A virus (HAV) infection and patients with acute hepatitis E virus (HEV) infection admitted to the Military Medical Academy (MMA), Sofia, Bulgaria. A retrospective study was performed at MMA, between 1 January 2016 and 31 December 2021. The etiological diagnosis was confirmed by enzyme-linked immunosorbent assay (ELISA) HAV/HEV IgM serology assays. The current survey included 231 patients with mean age 45.11 ± 16.08 years (95% confidence interval: 43.04-47.19). According to the case definition, inclusion and exclusion criteria, persons were divided into two groups: patients with acute HAV infection (68.4%; 158/231) and patients with acute HEV infection (31.6%; 73/231). Males with HEV had 3.091 times the odds of comorbidity "hypertension" than males with HAV (p = 0.032). There were almost equal odds of increased ALT (odds ratio = 0.999; p = 0.003) in men with HEV and men with HAV. Females with HEV had 5.161 times the odds of comorbidity "hypertension" compared with females with HAV (p = 0.049). We found almost equal odds for elevated ALT in women with HEV and women with HAV (OR = 0.999; p = 0.025). In the non-elderly group (<60-year-old), HEV individuals had 4.544 and 10.560 times the odds of comorbidities "hypertension" and "cardiovascular diseases" compared with HAV patients (p < 0.05). We found almost equal odds for elevated ALT in HEV patients and HAV participants (OR = 0.998; p = 0.002). The results from the current study may support the physicians daily care for patients with acute HAV and acute HEV.

Paving the way for T cell-based immunotherapies in chronic hepatitis E

Hepatitis A and hepatitis E are not limited to tropical countries but are also present in industrialized countries. Both infections share similar clinical features. There is no comparative study evaluating the clinical parameters of autochthonous and imported hepatitis A virus and hepatitis E virus infections. The aim of this study was to determine differences between autochthonous and imported hepatitis A virus (HAV) and hepatitis E virus (HEV) infections. Medical charts of all patients at our center with acute HAV and HEV infections were analyzed retrospectively (n = 50, study period 01/2009 - 08/2013). Peak bilirubin (median 8.6 vs. 4.4 mg/dL, p = 0.008) and ALT levels (median 2998 vs. 1666 IU/mL, p = 0.04) were higher in patients with hepatitis A compared to hepatitis E. In comparison to autochthones hepatitis E cases, patients with imported infections had significantly higher peak values for AST, ALT, bilirubin and INR (p = 0.009, p = 0.002, p = 0.04 and p = 0.049, respectively). In HAV infection, AST levels tended to be higher in imported infections (p = 0.08). (i) It is not possible to differentiate certainly between acute HAV and HEV infections by clinical or biochemical parameters, however, HAV infections might be associated with more cholestasis and higher ALT values. (ii) Imported HEV infections are associated with higher transaminases, INR and bilirubin levels compared to autochthonous cases and (iii) imported HAV infections tend to be associated with higher transaminases in comparison to autochthonous cases.

The World Health Organization (WHO) estimates that every year hepa -titis A virus (HAV) infection causes nearly 1.4 million new cases worldwide and the hepatitis E virus (HEV) is re-sponsible for 20 million new infections and over 3 million acute cases. Although in most cases HAV and HEV infections are self-limiting, HAV is estimated to kill 100 000 people each year [1] and HEV nearly 60000 people annually [2]. Pregnant women are at risk of more severe disease, obstetric complications and increased mortality if infected in the third trimester of pregnancy. The faecal–oral route is a well-established mode of transmission for both HAV and HEV and in the case of HEV infec-tion person-to-person transmission is also an important factor in sporadic cases [3]. Outbreaks of HAV and HEV are therefore manifestations of the poor sanitation practices and lack of clean water supplies often found in developing countries. Humanitarian crises with large refugee populations can also be fertile ground for hepatitis outbreaks alongside cholera or other waterborne outbreaks, as was recently seen among Syrian refugees in Iraq [4]. Understanding the importance of the risk of hepatitis outbreaks in displaced populations can help in identifying out-breaks quickly and responding to them in a timely manner to reduce mortality and morbidity. HAV has 7 genotypes, with little variation in their clinical expression. HEV has 4 genotypes with quite differ-ent clinical expressions, responsible for different disease manifestations across developing and developed countries. In developing countries genotype 1 is largely responsible for outbreaks and sporadic cases, via contamination of water and the fecal–oral route. Excep-tions include Mexico in South America and countries in Africa, where genotype 2 is more common [5]. Neither HAV nor HEV have chronic states, although HEV is reported in immunocompro-mised people [6]. Acute HAV infection is often clini-cally indistinguishable from other caus-es of acute viral hepatitis, and laboratory confirmation is necessary. Diagnosis of HEV has its own challenges, which may result in an underestimation of the disease burden [6]. HAV has a very effective vaccine available, and the first vaccine for HEV was approved in China in December 2011, although it is not yet used in any other countries. Whereas HAV seroprevalence increases with age and comes close to 100% in highly endemic countries by the age of 5 years, HEV seroprevalence tends to stay be-tween 5%–60% [7]. In 2010, the WHO World Health Assembly adopted resolution WHA63.18, which called for the pre-vention and control of viral hepatitis, with a focus on HBV and HCV [8]. This resolution came after Member States and WHO understood the gravity of spread of viral hepatitis. In 2012, on the occasion of World Hepatitis Day, Dr Ala Alwan, WHO Regional Director for the Eastern Mediterranean, urged all stakeholders to combine their efforts to confront and combat this silent epi-demic of hepatitis. Many countries of the Eastern Mediterranean Region (EMR) are cur-rently going through major social and political upheavals. With active or proxy wars engulfing many countries in the Region, the public health structures are under stress, creating ideal conditions for the spread of all infectious diseases, especially those spread by contaminated water and lack of sanitation services. Except for a few published articles and outbreak reports, however, very limited data are available about the prevalence of HAV and HEV from these countries or from the Region in general [9–12]. One major reason for this knowledge gap is that we are not looking for the evidence. In most developing countries, including most of those of the EMR, HEV is not routinely considered when a physician asks for investigations into a suspected case of viral hepatitis. Added to the diagnostic challenges is the fact that a majority of hepatitis-infected per-sons do not develop an acute condition that requires major health care interven-tion. HAV is in the same class, with few symptomatic cases reaching health-care settings, and as it is self-limiting in most cases, it is neither investigated nor re-ported to surveillance systems as HAV. Physicians also do not consider HAV or HEV to be serious illnesses, even though fulminant hepatitis, hepatic failure and death can occur from both infections.More than 40% of the population of the EMR lives in just 2 countries, Egypt and Pakistan, both of which are consid-ered endemic for HBC and HCV [8]. In Pakistan, the Field Epidemiology Labo-ratory Training Programme is collecting information about acute viral hepatitis cases via 5 sentinel sites throughout the country [13]. According to reports from the Pakistan viral hepatitis surveillance system HAV—responsible for more

BACKGROUND Hepatitis A &amp; E viruses are enterically transmitted viruses responsible for acute viral hepatitis in developing countries. Hepatitis A virus (HAV) has worldwide distribution while hepatitis E virus (HEV) is restricted to tropical countries. HAV affects infants and young children while HEV affects older children and young adults. This study was conducted to determine the seroprevalence of HAV and HEV and their co-infection in patients presenting with acute viral hepatitis (AVH). METHODS 200 sera of patients suffering from suspected acute viral hepatitis (AVH) attending tertiary care rural hospital JNMC Sawangi, Wardha were included in the study. Serum samples were tested for IgM anti HAV and IgM anti - HEV for the detection of acute hepatitis A and acute hepatitis E using commercially available ELISA kit &amp; Immunochromatography test (ICT) for comparison of ELISA and ICT. RESULTS The overall seroprevalence of HAV and HEV infection was found to be 19 %. The seroprevalence of HAV infection was found to be 13 %, HEV infection 5 % and HAV - HEV co - infection 1 %. HAV infection in males and females was found to be 16.07 % and 9.09 % respectively &amp; HEV infection was found to be 5.35 % and 4.54 % respectively. In case of detection of HAV IgM, two serum samples were negative by ICT but positive by ELISA &amp; for HEV IgM, one serum sample was negative by ICT but positive by ELISA. The sensitivity, specificity, positive predictive value and negative predictive value of HAV IgM was found to be 96 %, 98.8 %, 92.30 % &amp; 99.43 % and for HEV IgM was found to be 90 %, 99.47 %, 90 % &amp; 99.47 % respectively. CONCLUSIONS It is evident from this study that infection with enteric hepatitis viruses is not infrequent. Findings from this study emphasize the need to establish regular seroepidemiological surveys to keep track of epidemiology of these viruses. Results from rapid tests are comparable to ELISA with additional advantage of ease of interpretation and neither time consuming nor requiring special instruments. KEY WORDS Hepatitis A, Hepatitis E, Seroprevalence

Introduction

Pathogenesis and Treatment of Hepatitis E Virus Infection

Chronic hepatitis E in the immunosuppressed: A new source of trouble?

Objective: Acute viral hepatitis (AVH) in children is a serious and major public health concern globally and in developing countries such as Pakistan. We conducted this study to determine the clinical and epidemiological spectrum of AVH due to hepatitis A virus (HAV) and hepatitis E virus (HEV) infection in children.Methodology: This cross-sectional study was conducted at the Pediatric Medicine Department of a tertiary care hospital from February 20, 2020, to February 20, 2022. A total of 200 children 1-12 years of age who presented with symptoms and signs of AVH were enrolled. Demographic and clinical characteristics were noted, and venous blood was drawn for the assessment of HAV IgM and HEV IgM using an enzyme-linked immunosorbent assay (ELISA). Descriptive statistics are run, and the results are presented as tables.Results: Of the children, 75% were diagnosed with acute HAV infection. The median duration of illness was six days (range: 2-21 days). The most common age group affected was 6-10 years (43.5%), of which 56.5% were males. Most of the children belonged to low and middle socioeconomic status (86.5%), and 41.5% consumed underground water for drinking. Fever was the most common symptom, followed by appetite loss and yellow discoloration of urine. Alanine aminotransferase (ALT) was significantly high in HEV compared to HAV infection (2060.2±1036.7 versus 1730.7±957.5 IU/L) (P=0.04).Conclusion: Acute HAV was more prevalent. Those who are male, 6-10 years of age, from lower and middle socioeconomic status, and using underground drinking water were more affected by acute viral hepatitis. The clinical and biochemical presentation of HAV and HEV did not differ significantly.

ObjectiveTo conduct surveillance for acute Hepatitis A virus (HAV) infections in Veterans from states reporting outbreaks among high-risk individuals beginning in fiscal year (FY) 2017.IntroductionAlthough cases of acute HAV have declined in recent years, elevated numbers of HAV infections began to be reported by California and Michigan in the fall of 2016.1,2 Since this time, associated outbreaks have been reported in 9 additional states (Arizona, Utah, Kentucky, Missouri, Tennessee, Indiana, Ohio, Arkansas, and West Virginia).3 No common source of food, beverages or drugs have been identified and transmission appears to be primarily person-to-person with high-risk individuals including people experiencing homelessness, those who use illicit drugs and their close direct contacts. In June 2018, CDC issued a Health Alert Network Advisory providing additional guidance on identification and prevention of HAV and updates on the outbreaks.4 This prompted our office to more closely review our HAV surveillance, to identify Veterans who may be part of these outbreaks, and assess risk factors and outcomes of HAV infection.MethodsWe queried VA data sources starting in FY 2017 (October 1, 2016 – June 30, 2018) for HAV IgM laboratory tests and HAV-coded outpatient encounters and hospitalizations (ICD-10-CM: B15) to identify potential case patients. We performed a detailed chart review on all HAV IgM positive Veterans residing in or treated in an outbreak state during the identified outbreak time frame as reported by each state health department. Data elements collected included: (1) demographics; (2) risk factors, exposures and Hepatitis A vaccination status; (3) treatment locations (i.e. outpatient, Emergency Department, inpatient, intensive care unit); (4) presenting signs and symptoms; (5) laboratory data (including liver function tests (LFTs) and hepatitis testing); and (6) outcomes (i.e. deaths). County-level rates for positive HAV IgM test results were calculated using total unique users of VHA care for matching fiscal year time frames in each county as denominators.ResultsA total of 247 HAV IgM positive individuals were identified among 136,970 HAV IgM tests performed during the study period. Among these, 67 individuals resided in an outbreak state and were identified for further chart review. Additional laboratory review revealed that 5 of the 67 were positive for HAV Total Ab with no HAV IgM performed (all five patients came from a single facility and were asymptomatic at the time of testing). Based on review of clinical data for the remaining 62 HAV IgM positive patients, 22 (35%) did not meet the CSTE clinical case definition criteria5 of having signs or symptoms consistent with acute viral hepatitis plus either jaundice or elevated ALT/AST levels. These patients were either asymptomatic or had relevant symptoms that could be explained by other diagnoses. None had documented jaundice and only 4 had any LFT elevation, which was mild (ALT: 60-83 IU/L, AST: 36-103 IU/L). There was often no mention of the positive HAV IgM test result in the patient visit records. In the cases where the results were documented, it was thought to be a false positive or cross reactivity, related to recent receipt of HAV vaccination, or prolonged persistence of HAV IgM from a prior infection. Patient characteristics of the 40 patients meeting the case definition are summarized in Table 1. None of confirmed cases had documentation of HAV vaccination prior to their acute infection. The top 5 counties of residence among confirmed cases were Jefferson, KY (7, 18%), San Diego, CA (6, 15%), Wayne, MO (4, 10%), Butler, MO (3, 8%) and Macomb, MI (3, 8%). Additionally, the top three counties (Jefferson, San Diego and Wayne) were each noted to have clustering of cases of acute HAV with risk factors of homelessness, substance abuse and/or needle exposure. Incidence rates for HAV IgM+ test results were calculated for all reported outbreak counties and the 25 counties with the highest rates are shown in Figure 1.ConclusionsOccurrence of acute HAV infections among Veterans during October 2016 – June 2018 followed patterns reported by states with outbreaks during the same time frame, including high hospitalization rates. Risk factors of homelessness, substance abuse and/or needle exposures were noted in the Veteran population, similar to national HAV outbreak data. County-level clustering of cases in states with outbreaks was also observed among Veterans, with incidence rates of HAV IgM+ as high as 13 per 10,000 Veterans. Additional education of VA providers is needed regarding recognition of and appropriate testing for acute HAV infections. HAV IgM should not be ordered in asymptomatic patients with normal LFTs as the pretest probability of HAV infection is low, leading to false positives and confusion in interpreting test results. Improving Hepatitis A vaccination rates among Veterans is important, particularly among individuals who are at increased risk for infection or complications from HAV and in outbreak states to limit further spread of this outbreak.

Introduction: Enterically transmitted Hepatitis A Virus (HAV) and Hepatitis E Virus (HEV) are the most common cause of Acute Viral Hepatitis (AVH) and a major health concern in developing nations like India. Both viruses cause AVH and are spread predominantly through the faecal-oral pathway, most commonly through contaminated water. Aim: To estimate the prevalence of HAV and HEV infection in patients presenting with AVH. Materials and Methods: An analytical cross-sectional study was undertaken in Indira Gandhi Institute of Medical Sciences, Bihar. The study was conducted over a period of 24 months from November 2019 to October 2021. All patients presenting with AVH were included as study participants. The blood samples were subjected to test anti-HAV and anti-HEV positivity. Prevalence of HAV and HEV was calculated taking total cases of AVH as denominator. Patients with confirmed infection with HCV, HBV and any other cause of hepatitis were excluded from the study. Templates were generated in an Microsoft Excel spreadsheet and analysis of data was done using Statistical Package of the Social Sciences software (SPSS) version 20.0. Quantitative data were presented as frequency and percentages. Results: A total of 682 patients presented with acute hepatitis. The AVH patients comprised 467 males (68.5%) and 215 (31.5%) females with the mean age 39.6±18.87 years. The current study reports the seroprevalence of 9.18% HAV and 8.35% of HEV. A total of 4 patients tested positive for coinfection with HAV and HEV. Most of the HAV patients belonged to an age group less than or equal to 12 years (25,58.1%) and none were more than 60 years. However, none of the HEV patients were children and most of them were aged between 13 to 60 years (46,92%). A male preponderance among HAV (28,65.1%), and HEV (38,76%) was noted. Conclusion: Low seroprevalence was noted, with infection more common in younger age group and male patients. Further studies and vaccination along with surveillance system strengthening are warranted.

Objectives: Hepatitis A virus (HAV) and hepatitis E virus (HEV) infections are significant global health concerns that contribute to acute viral hepatitis. This study aimed to investigate the prevalence of HAV, HEV, and co-infections in a tertiary care hospital setting in central India. Materials and Methods: This retrospective observational study analyzed 987 clinical specimens collected from suspected acute viral hepatitis cases over 5 years (2019–2023). Commercially available enzyme-linked immunosorbent assay kits were used to detect HAV and HEV immunoglobulin M antibodies. Statistical analysis: Demographic data and clinical information were collected and analyzed using Chi-square tests. P &lt; 0.05 was considered statistically significant, indicating a significant association between the variables under investigation. Results: Overall, 32.72% of patients were seropositive for either HAV, HEV, or both. The prevalence of HAV was 22.9%, HEV was 9.83%, and co-infection was 3.24%. HAV infection was more prevalent in children (0–14 years), whereas HEV was more prevalent in adults. Both HAV and HEV infections were associated with elevated liver function markers, with the highest levels observed in co-infected cases. The monsoon season had the highest number of cases. Conclusions: This study revealed a substantial burden of HAV, HEV, and co-infections in central India. The observed sex—and age-specific prevalence patterns warrant further investigation. Effective public health strategies addressing sanitation, hygiene practices, and HAV vaccination programs are crucial to reducing the disease burden.

Viral hepatitis is the general term for inflammatory disease of the liver caused by at least five different viruses, with hepatitis A, B, C, D, and E viruses having a definite association with acute viral hepatitis. Of these, only hepatitis A virus (HAV) and hepatitis E virus (HEV) are enterically transmitted, and both cause acute and generally self-limiting infections without significant long-term carrier status. While there are no serious long-term sequelae in patients who recover from hepatitis A or hepatitis E, both viruses are associated with significant risks of acute, fulminant hepatitis and liver failure, and chronic hepatitis E has been reported in immunosuppressed patients. Severe outcomes are most commonly seen in patients with acute hepatitis A who also have chronic hepatitis C or hepatitis B infection, and also in patients with acute hepatitis E during pregnancy, especially during the third trimester. In the absence of these cofactors, the diseases show a general trend towards greater severity with increasing age, with the majority of infections being subclinical in children; however, severe and fulminant hepatitis A and E infections can occur at any age. In many developed countries, HEV infection is rare and HAV infection rates have declined, making recognition and diagnosis more challenging. This chapter discusses recent advances in our understanding of HAV and HEV infections, including diagnostic testing and interpretation.