UNASSIGNED: The prevalence of hepatitis B in the Republic of Korea has declined, yet the disease burden persists. After various changes in targets and methods, the national hepatitis B surveillance system now exclusively monitors acute cases. We aimed to assess the alignment of this system with its intended purpose and to recommend improvements supporting the national strategic plan for viral hepatitis management.
UNASSIGNED: This study assessed acute hepatitis B cases reported to the Korean Disease Control and Prevention Agency\'s mandatory surveillance system over a 10-year period (2013-2022). It evaluated 5 factors from the Centers for Disease Control and Prevention\'s Updated Guidelines for Evaluating Public Health Surveillance Systems: simplicity, positive predictive value, data quality, timeliness, and usefulness.
UNASSIGNED: The nonspecific nature of acute hepatitis B symptoms, along with the complexity of diagnostic criteria, indicated a high potential for misreporting. The surveillance system demonstrated a high positive predictive value (94.4%), with data quality and timeliness also rated high. However, data following the onset of the coronavirus disease 2019 pandemic indicate the need for improvement. Moreover, given the relative importance of specific characteristics of chronic infectious diseases, only limited interventions are implementable through the current surveillance system.
UNASSIGNED: The evaluation of the Republic of Korea\'s acute hepatitis B surveillance system revealed high positive predictive value, data quality, and timeliness. However, improvements can be made in the misreporting of chronic cases and the system\'s usefulness. More accurate reflection of the characteristics of acute hepatitis B cases is essential for better management of viral hepatitis.

On March 31, 2022, severe acute hepatitis of unknown origin was first reported from the Royal Glasgow Children\'s Hospital in Scotland. According to the criteria by WHO-ECDC, a probable case of unknown acute hepatitis in children is defined as a subject under 16 years of age, who tested negative for viral hepatitis and transaminases >500 U/L, starting from the 1st of October 2021. WHO invites Member States to participate in the global effort to collect anonymized clinical data on probable cases of severe acute hepatitis of unknown aetiology. As of May 26, 2021, 650 cases were already registered on the platform worldwide, of whom at least 38 cases have required liver transplants. Several hypotheses such as previous SARS-CoV-2 infection or coinfection or infection with another virus were examined and a strong association was found between adenovirus (41F) and acute hepatitis of unknown aetiology cases. This review article summarizes the global epidemiological evidences on acute hepatitis of unknown origin in children, analysing their incidence and characteristics.

UNASSIGNED: Hepatocellular carcinoma (HCC) is the most common cancer in Mongolia. The relative importance of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in HCC etiology is known to vary greatly from one part of the world to another. Principally, 95% of HCC patients have chronic viral hepatitis, including 53% hepatitis B virus, 38.9% HCV, and 5.6% have HBV/HCV coinfection. Hepatitis D virus (HDV) infection is widely spread in our country, anti-HDV has been found in more than 25% of carriers who have HBsAg.
UNASSIGNED: We analyzed data of patients who had been diagnosed with acute viral hepatitis in the Department of adult hepatitis, National Center for Communicable Diseases in Mongolia from 1952 to 2018.
UNASSIGNED: A total of 318,831 cases of acute viral hepatitis were registered in Mongolia between 1981 and 2019, which is 34.9 cases per 10,000 population. Of these, 265,931 cases of acute viral hepatitis A, or 28.6 per 10,000 populations, 48,855 cases of acute viral hepatitis B, or 5.5 cases per 10,000 populations, and 2,607 cases of acute viral hepatitis C, or 0.4 cases per 10,000 populations were recorded.
UNASSIGNED: The prevalence of viral hepatitis in our country was the highest in 1981-1991, but since 2012, the prevalence of infection has steadily decreased. In Mongolia, since 1960, multifaceted programs and activities to combat viral hepatitis have been successfully implemented at the national level.
UNASSIGNED: Badamnachin B, Badamjav T, Dondov G, et al. The Dynamics of the Prevalence of Acute Viral Hepatitis and the Strategies against Viral Hepatitis in Mongolia. Euroasian J Hepato-Gastroenterol 2024;14(1):65-69.

BACKGROUND: An outbreak of acute severe hepatitis of unknown aetiology (AS-Hep-UA) in children during 2022 was subsequently linked to infections with adenovirus-associated virus 2 and other \'helper viruses\', including human adenovirus. It is possible that evidence of such an outbreak could be identified at a population level based on routine data captured by electronic health records (EHR).
METHODS: We used anonymised EHR to collate retrospective data for all emergency presentations to Oxford University Hospitals NHS Foundation Trust in the UK, between 2016-2022, for all ages from 18 months and older. We investigated clinical characteristics and temporal distribution of presentations of acute hepatitis and of adenovirus infections based on laboratory data and clinical coding. We relaxed the stringent case definition adopted during the AS-Hep-UA to identify all cases of acute hepatitis with unknown aetiology (termed AHUA). We compared events within the outbreak period (defined as 1st Oct 2021-31 Aug 2022) to the rest of our study period.
RESULTS: Over the study period, there were 903,433 acute presentations overall, of which 391 (0.04%) were classified as AHUA. AHUA episodes had significantly higher critical care admission rates (p < 0.0001, OR = 41.7, 95% CI:26.3-65.0) and longer inpatient admissions (p < 0.0001) compared with the rest of the patient population. During the outbreak period, significantly more adults (≥ 16 years) were diagnosed with AHUA (p < 0.0001, OR = 3.01, 95% CI: 2.20-4.12), and there were significantly more human adenovirus (HadV) infections in children (p < 0.001, OR = 1.78, 95% CI:1.27-2.47). There were also more HAdV tests performed during the outbreak (p < 0.0001, OR = 1.27, 95% CI:1.17-1.37). Among 3,707 individuals who were tested for HAdV, 179 (4.8%) were positive. However, there was no evidence of more acute hepatitis or increased severity of illness in HadV-positive compared to negative cases.
CONCLUSIONS: Our results highlight an increase in AHUA in adults coinciding with the period of the outbreak in children, but not linked to documented HAdV infection. Tracking changes in routinely collected clinical data through EHR could be used to support outbreak surveillance.

OBJECTIVE: This study aimed to assess metabolic changes to monitor the progression from normal liver to hepatitis B virus (HBV)-related hepatitis and liver fibrosis using hyperpolarized 13C magnetic resonance imaging (MRI).
METHODS: Hepatitis was induced in mice (n = 16) via hydrodynamic injection of HBV 1.2 plasmid (25 μg). Among them, liver fibrosis was induced in the mice (n = 8) through weight-adapted administration of thioacetamide with ethanol. Normal control mice (n = 8) were injected with a phosphate buffer solution. Subsequently, a hyperpolarized 13C MRI was performed on the mouse liver in vivo. The level of hepatitis B surface antigen (HBsAg) in blood serum was measured. Statistical analysis involved comparing the differential metabolite ratios, blood biochemistry values, and body weight among the three groups using the Kruskal-Wallis one-way analysis of variance.
RESULTS: HBsAg was absent in the normal and fibrosis groups, while it was detected in the hepatitis group. The ratios of [1-13C] lactate/pyruvate, [1-13C] alanine/pyruvate, [1-13C] lactate/total carbon, and [1-13C] alanine/total carbon were significantly lower in the normal control group than in the hepatitis and fibrosis groups (p < 0.05). Moreover, these ratios were significantly higher in the fibrosis group than in the hepatitis group (p < 0.05). However, no significant differences were observed in either [1-13C] pyruvate-hydrate/pyruvate or [1-13C] pyruvate-hydrate/total carbon among the three groups.
CONCLUSIONS: The levels of [1-13C] lactate and [1-13C] alanine in vivo may serve as valuable indicators for differentiating between HBV-related hepatitis, liver fibrosis, and normal liver.

BACKGROUND: Outbreaks of acute hepatitis of unknown etiology (AHUE) in children were reported in Western countries in 2022. Previous studies found that adeno-associated virus 2 (AAV2) and its helper viruses, such as human adenovirus (HAdV) and human herpesvirus-6 (HHV-6), are frequently detected in patients with AHUE. However, the existence of hepatitis associated with AAV2 prior to AHUE outbreaks in 2022 had not yet been investigated. We aimed to investigate the association between AAV2 and pediatric acute hepatitis in Japanese children, as well as the incidence of AAV2-related hepatitis prior to 2022.
METHODS: Preserved blood samples obtained from 49 pediatric patients with acute hepatitis between 2017 and 2023 were retrospectively analyzed. Blood samples from 50 children with acute illnesses and 50 children with chronic conditions were used as controls. Viral DNA loads were quantitated using real-time PCR.
RESULTS: AAV2 DNA was detected in 12 % (6/49) of acute hepatitis cases but in only one acute illness and none of the chronic-condition control cases. The concentration of AAV2 DNA in the six acute hepatitis cases was higher than that in the acute-illness control case. Co-infection with one or more helper viruses, including HAdV, HHV-6, cytomegalovirus, and Epstein-Barr virus, was observed in five AAV2-positive cases.
CONCLUSIONS: Our results indicated the sporadic occurrence of pediatric severe hepatitis associated with AAV2 infection in Japan prior to the AHUE outbreaks in 2022. Our findings suggest that co-infection with AAV2 and helper viruses plays a role in developing severe hepatitis.

The prevalence of liver disease is rising and more patients with liver disease are considered for surgery each year. Liver disease poses many potential complications to surgery; therefore, assessing perioperative risk and optimizing a patient\'s liver health is necessary to decrease perioperative risk. Multiple scoring tools exist to help quantify perioperative risk and can be used in combination to best educate patients prior to surgery. In this review, we go over the various scoring tools and provide a guide for clinicians to best assess and optimize perioperative risk based on the etiology of liver disease.

OBJECTIVE: The majority of indeterminate pediatric acute liver failure (PALF) cases are secondary to immune dysregulation, labeled activated T-cell hepatitis (TCHep). We aimed to describe a cohort of children with acute severe hepatitis and PALF and define how clinical immune labs may help identify the TCHep group.
METHODS: Retrospective review of children with acute hepatitis and PALF between March 2020 and August 2022. Patients were classified as known diagnosis, indeterminate hepatitis (IND-Hep), or TCHep (defined by liver biopsy with predominant CD8 T-cell inflammation or development of aplastic anemia).
RESULTS: 124 patients were identified: 83 with known diagnoses, 16 with TCHep, and 25 with IND-Hep. Patients with TCHep had significantly increased median total bilirubin levels (7.5 mg/dL (IQR 6.8-8.9) vs 1.5 mg/dL (IQR 1.0-3.6), p < 0.0001), soluble interleukin-2 receptor levels (4512 IU/mL (IQR 4073-5771) vs 2997 IU/mL (IQR 1957-3237), p = 0.02), and percent of CD8+ T-cells expressing perforin (14.5 % (IQR 8.0-20.0) vs 1.0 % (IQR 0.8-1.0), p = 0.004) and granzyme (37.5 % (IQR 15.8-54.8) vs 4.0 % (IQR 2.5-5.5), p = 0.004) compared to IND-Hep patients. Clinical flow cytometry showed that TCHep patients had significantly increased percent CD8+ T cells (29.0 % (IQR 24.5-33.5) vs 23.6 % (IQR 19.8-25.8), p = 0.04) and HLA-DR+ (16.0 % (IQR 14.5-24.5) vs 2.7 (1.8-5.3), p < 0.001) compared to IND-Hep patients indicative of increase in CD8+ T cells that are activated.
CONCLUSIONS: Peripheral blood clinical immune studies demonstrate increased markers of CD8 T-cell activation, proliferation, and cytotoxic function for TCHep patients. These readily available immune function labs can be used to help distinguish patients with TCHep from those with other causes. This provides a non-invasive tool for early detection of potential TCHep before progression to liver failure.

Liver biopsies have consistently contributed to our understanding of the pathogenesis and aetiologies of acute liver disease. As other diagnostic modalities have been developed and refined, the role of biopsy in the management of patients with acute liver failure (ALF), acute-on-chronic liver failure (ACLF) and acute hepatitis, including acute liver injury (ALI), has changed. Liver biopsy remains particularly valuable when first-line diagnostic algorithms fail to determine aetiology. Despite not being identified as a mandatory diagnostic tool in recent clinical guidelines for the management of ALF or ACLF, many centres continue to undertake biopsies given the relative safety of transjugular biopsy in this setting. Several studies have demonstrated that liver biopsy can provide prognostic information, particularly in the context of so-called indeterminate hepatitis, and is extremely useful in excluding conditions such as metastatic tumours that would preclude transplantation. In addition, its widespread use of percutaneous biopsies in cases of less severe acute liver injury, for example in the establishment of a diagnosis of acute presentation of autoimmune hepatitis or confirmation of a probable or definite drug-induced liver injury (DILI), has meant that many centres have seen a shift in the ratio of specimens they are receiving from patients with chronic to acute liver disease. Histopathologists therefore need to be equipped to deal with these challenging specimens. This overview provides an insight into the contemporary role of biopsies (as well as explant and autopsy material) in diagnosing acute liver disease. It outlines up-to-date clinical definitions of liver injury and considers recent recommendations for the diagnosis of AIH and drug-induced, autoimmune-like hepatitis (DI-AIH).

Pediatric acute liver failure is a rare but serious complication of Coronavirus infections. Our patient is a previously healthy 8-year-old male who presented with acute liver failure in the setting of human coronavirus HKU1 (HCoV-HKU1) infection while asymptomatic from a respiratory perspective. During the hospital course, he developed acute hepatic encephalopathy and was listed for liver transplantation, but fortunately recovered remaining status 7 (inactive) on the transplant list. With a negative diagnostic evaluation other than his viral infection and hyperdense CD8 T-cells on liver immunohistochemical staining, pediatric acute liver failure (PALF) immune dysregulation phenotype was diagnosed.