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In April 2023, an outbreak of acute hepatitis was reported amongst internally displaced persons in the Nazareth community of South Sudan. IgM serology-based screening suggested the likely etiologic agent to be Hepatitis E virus (HEV). In this study, plasma specimens collected from anti-HEV IgM-positive cases were subjected to additional RT-qPCR testing and sequencing of extracted nucleic acids, resulting in the recovery of five full and eight partial HEV genomes. Maximum likelihood phylogenetic reconstruction confirmed the genomes belong to HEV genotype 1. Using distance-based methods, we show that genotype 1 is best split into three sub-genotypes instead of the previously proposed seven, and that these sub-genotypes are geographically restricted. The South Sudanese sequences confidently cluster within sub-genotype 1e, endemic to northeast, central, and east Africa. Bayesian Inference of phylogeny incorporating sampling dates shows that this new outbreak is not directly descended from other recent local outbreaks for which sequence data is available. However, the analysis suggests that sub-genotype 1e has been consistently and cryptically circulating locally for at least the past half century and that the known outbreaks are often not directly descended from one another. The ongoing presence of HEV, combined with poor sanitation and hygiene in the conflict-affected areas in the region, place vulnerable populations at risk for infection and its more serious effects, including progression to fulminant hepatitis.

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This is the case of a 25-year-old patient, with the notion of unprotected sexual relations with multiple partners consulted for cholestatic icterus with pruritus evolving for 2 months. The general examination found an intense mucocutaneous icterus. The examination of the lymph nodes revealed multiple lymph nodes. A thoracic-abdominal-pelvic scanner showed peri-portal edema and adenopathies above and below the diaphragm without suspicious lesions. Biologically, there was acute cytolysis with ASAT at 1612IU/L, ALAT at 1506IU/L, and icteric cholestasis, the acute viral serologies and other autoantibodies were all negative. Given the presence of adenopathy and sexual risk factors, a syphilis serology was requested and was positive: a TPHA at 2560UI/L, and a VDRL at 1/32 UI/L. A liver biopsy was performed, which showed the presence, on immunohistochemistry, of anti-treponemal-pallidum antibodies. After eliminating all etiologies of cytolytic hepatitis, we retained the diagnosis of syphilitic hepatitis. Therapeutically, we started a treatment based on ceftriaxone 2g/dl with spectacular biological improvement at H48 of the beginning of treatment.

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BACKGROUND: Acute hepatitis E infection (HEV), with its high incidence in Europe, should be considered as a differential diagnosis of acute viral hepatitis and can in some cases manifest with pronounced neurological symptoms. CLINICAL CASE: We report on a 33-year-old female patient with severe arthralgia, myalgia, headache and psychomotor deterioration. Laboratory analyses showed elevated transaminases without signs of cholestasis. Acute hepatitis E virus infection was detected in serum. She reported fatigue and dysesthesias not responsive to analgesics. Cerebrospinal fluid (CSF) analysis revealed an inflammatory syndrome. HEV RNA was detected in the CSF. The infection remained mild, but dysesthesias persisted. Eight weeks after the first admission, the symptoms worsened again. Complete and sustained remission was achieved following intravenous corticosteroid treatment. CONCLUSION: In patients with acute neurological symptoms and liver enzyme elevation, HEV infection should be considered. Neurologic symptoms such as fatigue, arthralgia, myalgia and dysesthesia along with psychomotor retardation should prompt CSF analysis.

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BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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BACKGROUND & AIMS: Acute hepatitis E (AHE) poses a significant threat to global public health, particularly among women of childbearing age (WCBA), who are at heightened risk for severe pregnancy-related complications. This study aimed to delineate the temporal trends and project future incidence of AHE in WCBA, providing insights crucial for targeted prevention and control strategies. METHODS: Data on AHE incidence from the Global Health data 2021. The age-period-cohort (APC) model was applied to analyze trends across different age groups, periods, and birth cohorts, and the Bayesian APC model was utilized for forecasting future epidemiological trajectories. RESULTS: Globally, AHE incidence numbers among WCBA rose from 2,831,075 in 1992 to 3,420,786 in 2021, while the age-standardized incidence rate (ASIR) declined from 194.66 to 179.54 per 100,000 with a global net drift of -0.28%. However, high SDI regions showed a contrasting trend with a positive net drift of 0.02%. The age effect was consistent across SDI regions and globally, showing a decrease with advancing age, while unfavorable period and cohort effects were exhibited in high-SDI region. At the national level, locations exhibited varying trends of change. The BAPC model predicted a total of 3,759,384 AHE global cases in WCBA by 2030, with an expected mild increase in the ASIR. The outlook for the management and containment of AHE is grim in certain countries, including India. CONCLUSIONS: The study revealed a complex epidemiological landscape of AHE in WCBA, with increasing global incidence numbers juxtaposed against a declining ASIR. The AHE burden by 2030 remain severe among WCBA. Young WCBA and high SDI region merit particular attention. The findings underscore the need for region-specific strategies to curb the projected rise in AHE incidence and align with the 2030 WHO goals.

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We diagnosed six cases of acute hepatitis C virus (HCV) infection at our hospital between October 2003 and December 2022. During the same period, we diagnosed 402 cases of chronic HCV infection and 636 cases of acute hepatic injury. Acute HCV infection cases accounted for 1.4% of all HCV infections and 0.9% of all acute hepatic injury cases. The acute HCV infection group was younger, had more severe hepatitis, and exhibited higher levels of bilirubinemia compared to the chronic HCV infection group. Two acute HCV infection cases achieved spontaneous viral clearance, while the remaining four cases progressed to chronic infection and were treated with direct-acting antivirals (DAAs). Liver enzyme elevation and liver function deterioration did not differ significantly between the acute HCV and other acute liver injury groups. Notably, DAA treatment was equally effective for acute and chronic HCV cases (75% vs. 90%, p = 0.34). Early DAA treatment in acute cases might contribute to interrupting viral transmission among high-risk populations, such as people who inject drugs or men who have sex with men. While there are currently no specific guidelines for acute HCV infection treatment in Japan, our findings suggest that DAA therapy should be initiated immediately following diagnosis. Further studies with larger patient cohorts are warranted to confirm these observations.

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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.

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Background: 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. Materials and methods: 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. Results: 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. Conclusion: 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. How to cite this article: 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.

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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.

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INTRODUCTION: 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.

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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.

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AIM: To analyse clinical, laboratory, and epidemiological data of a cohort of patients with acute hepatitis E treated at the Clinic of Infectology and Travel Medicine (CITM) in Kosice. MATERIAL AND METHODS: Retrospective analysis of hospital information system data on patients diagnosed with acute hepatitis E who were examined or hospitalized at CITM in 2015-2023. Statistical evaluation of the available data with a focus on epidemiology, course, and complications. RESULTS: The cohort consisted of 62 patients. Fifty-eight percent were male. The mean age was 56 years. Seventy-four percent of patients were hospitalized, with a mean length of hospital stay of 10 days. The most common clinical manifestation was jaundice (in 40% of patients). Six patients had stool HEV RNA testing and all were confirmed to have genotype 3. In 5% of patients, the infection was classified as imported (they did not have HEV RNA tested), and 95% of cases were autochthonous. A history of contact with an HEV infected person was reported by 26% of patients. A history of preexisting liver disease was noted in 13% of patients who were confirmed with higher bilirubin, GMT, and ammonia levels. No statistically significant differences were found for patients with a history of immune deficiency. One patient with preexisting liver disease developed fulminant infection resulting in death. Four hepatitis E patients with neurological symptoms had lower bilirubin levels. CONCLUSIONS: The study cohort included predominantly older men. Genotype 3 was confirmed in all patients who underwent HEV RNA testing. Higher bilirubin, ammonia, and GMT levels were confirmed in patients with preexisting liver disease. Patients with neurological complications had lower bilirubin levels. One patient with preexisting liver disease died.

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PURPOSE: 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). PROCEDURES: 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.

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BACKGROUND AND AIMS: 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.

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Introduction: Hepatitis B vaccination was nationally funded for adolescents in 1996, with inclusion of universal infant immunisation under the National Immunisation Program (NIP) in May 2000. This study describes hepatitis B epidemiology in Australia in the two decades since 2000. Methods: This article analyses newly-acquired (within the prior 24 months) and unspecified (all other) hepatitis B notifications (2000-2019) from the National Notifiable Diseases Surveillance System; acute hepatitis B hospitalisations (2001-2019) from the National Hospital Morbidity Database; and acute (2000-2019) and chronic (2006-2019) hepatitis B deaths from the Australian Bureau of Statistics and Australian Coordinating Registry. Rates over the reporting period were described overall, and by age group, sex, and Aboriginal and Torres Strait Islander status (Aboriginal and/or Torres Strait Islander versus other [neither Aboriginal nor Torres Strait Islander, unknown or not stated]). Trend analyses were performed using Poisson or negative binomial regression. Additional analyses were performed for the cohort born after May 2000. Results and discussion: The annual all-age notification rate per 100,000 per year declined (p < 0.001) from 2.13 in 2000 to 0.65 in 2019 for newly-acquired hepatitis B and from 38.3 to 22.3 for unspecified hepatitis B (likely to predominantly represent chronic hepatitis B). Newly-acquired and unspecified hepatitis B notification rates were lowest among children aged < 15 years. The most substantial reductions in notification rates of newly-acquired hepatitis B were among adolescents aged 15-19 years and young adults aged 20-24 and 25-29 years (respectively 17-, 11-, and 7-fold); these age groups also recorded the most substantial reductions in unspecified hepatitis B notifications (respectively 5-, 3.5-, and 2-fold). Newly-acquired hepatitis B notification and acute hepatitis B mortality rates were two- to threefold higher in males than females. The all-age newly-acquired hepatitis B notification rate in Aboriginal and Torres Strait Islander people decreased twofold between 2000 and 2019, but remained threefold higher than in other people. Acute hepatitis B hospitalisations also declined over the study period (p < 0.001) and followed similar patterns. There were no acute or chronic hepatitis B deaths among people born after May 2000; this cohort featured 52 newly-acquired and 887 unspecified hepatitis B notifications. Due to lack of data on country of birth (and hence eligibility for infant vaccination under the NIP or overseas programs), vaccination status and likely transmission routes, we were unable to assess factors contributing to these potentially preventable infections. Conclusion: Adolescent and infant immunisation under the NIP has led to significant reductions in notification rates of newly-acquired hepatitis B, and in acute hepatitis B hospitalisation rates, both overall and in Aboriginal and Torres Strait Islander people. Unspecified hepatitis B notification rates have also greatly decreased in children and young adults, likely largely due to the impact of overseas infant immunisation programs on prevalence in child and adolescent migrants. Work to improve completeness of variables within national datasets is crucial, along with enhanced surveillance of both newly-acquired and unspecified hepatitis B cases to investigate transmission routes, vaccination status and factors contributing to acquisition of hepatitis B, in order to optimise the impact of immunisation programs and ensure linkage with care.

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Human adenovirus type 41 (HAdV-F41) usually causes pediatrics gastroenteritis. However, it was reported to be associated with the outbreaks of severe acute hepatitis of unknown aetiology (SAHUA) in pediatrics during COVID-19 pandemic. In this study, we investigated the prevalence of enteric HAdV-F41 in 37,920 paediatric gastroenteritis cases from 2017 to 2022 in Guangzhou, China. All children presented were tested negative for SARS-CoV-2 during the "zero-COVID" period. The main clinical symptom of the children was diarrhea (96.5%). No fatalities nor liver abnormal symptoms was found. In 2021, one year since the pandemic of COVID-19, the prevalence of HAdV-F41 abruptly increased from 3.71% to 8.64% (P < 0.001). All of HAdV-F41 circulating worldwide were classified into eight different subtypes (G1-G8) based on the phylogenetic clustering permutation of the four capsid genes of HAdV-F41. G3 was the predominant subtype (56.2%; 77/137). CRV5 isolates from SAHUA cases belong to this subtype, in which N312D and H335D mutations in the short fiber knob were identified in both Guangzhou and CRV5 isolates, presumably changing the virus tropism by directly interacting with the heparin sulfate (HS) receptor. Additionally, a novel recombinant G6 subtype, which is unique and only circulating in China was first identified in this study. This is the first study highlighting the prevalence of HAdV-F41 in paediatric cases of gastroenteritis during COVID-19 pandemic in China. The clinical and viral evolution finding of HAdV-F41 provide insight into the clinical characteristics of children with HAdV-F41 infections as well as the uncertain role of HAdV-F41 in the cause of SAHUA.

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BACKGROUND AND AIMS: An increase in the number of cases of acute hepatitis of unknown origin (HUO) in children was observed in 2021. Adenovirus and adeno-associated virus 2 (AAV2) infections have been suggested as possible triggers. However, the potential etiology is still unclear. We aimed to characterize a cohort of children with HUO in Israel in view of the COVID-19 pandemic. METHOD: Demographics, clinical data, and laboratory results on the children compatible with the CDC criteria for HUO were collected by the established registry of the Ministry of Health. Available specimens were sent to the Central Virology Laboratory. RESULTS: A total of 39 children were included in the registry. A total of 20 were enrolled prospectively, in which human herpes virus 6 (HHV6) infection or reactivation was identified in 11/19, adenovirus was found in 4/19 of the cases, and AAV2 was detected in 2/16. Past COVID-19 exposure was recorded for 24/39 of the children. A total of 10 children underwent liver biopsy, and 8 were successfully treated with steroids and 2 underwent liver transplantation. CONCLUSIONS: The COVID-19 pandemic and the related containment measures combined with reactivation or active infection with other viruses could have been a trigger for the HUO outbreak. In our cohort, HHV6 was the most abundant finding.

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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.

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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).

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Background: Serine/threonine kinase 1 (PIM1) plays a crucial role in cell growth, differentiation, and apoptosis. However, its role in the pathogenesis of concanavalin A (ConA)-induced acute hepatitis is not well understood. PIM1 kinase inhibitor can reduce the expression of PIM1. This study aims to investigate the effects of PIM1 kinase inhibitor and its protective mechanism in ConA-induced acute hepatitis. Methods: C57/BL six mice were injected with ConA (20, 15, and 12 mg/kg) to induce acute hepatitis, and PIM1 kinase inhibitor SMI-4a (60 mg/kg) was administered orally 24 h before ConA injection. The survival rate of the mice was observed after ConA injection. The levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured. Serum inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining was performed on liver tissue collected at different time points. The major cytokines expression in liver tissue was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The number of macrophages, T-cell and neutrophils in liver tissue were detected by flow cytometry (FCM). PIM1 in liver tissue was detected by western blot (WB) and qRT-PCR. SMI-4a (80 µM) was pretreated for 24 h and ConA (400 µg/mL) was stimulated for 12 h in RAW264.7 cell model. Phosphorylated p65 (p-p65) and cleaved caspase-3 (c-caspase-3) in liver tissue and macrophages were detected by WB. Results: Different concentrations of ConA caused different acute hepatitis mortality, 12 mg/kg concentration within 24 h of the mortality showed a gradient increase. The levels of AST and ALT increased significantly at 12 h after ConA injection. PIM1 expression was upregulated at 12 h. SMI-4a can suppress the PIM1 expression. SMI-4a suppressed cytokines production, AST, and ALT in ConA-treated serum. SMI-4a suppressed the major cytokines in liver tissue. Tests in liver tissue showed that SMI-4a reduced the number of T cells, neutrophils, and macrophages. SMI-4a inhibited the inflammatory response by downregulating the expression of p-p65. Meanwhile, apoptosis was decreased by decreasing the expression of c-caspase-3. Conclusions: In conclusion, the protective effect of SMI-4a against acute hepatitis is by reducing the inflammatory response and apoptosis. These findings suggest that SMI-4a may have therapeutic potential in the treatment of autoimmune hepatitis.