During the first half of 2022, the World Health Organization reported an outbreak of acute severe hepatitis of unknown aetiology (AS-Hep-UA) in children, following initial alerts from the United Kingdom (UK) where a cluster of cases was first observed in previously well children aged <6 years. Sporadic cases were then reported across Europe and worldwide, although in most countries incidence did not increase above the expected baseline. There were no consistent epidemiological links between cases, and microbiological investigations ruled out known infectious causes of hepatitis. In this review, we explore the evidence for the role of viral infection, superimposed on a specific host genetic background, as a trigger for liver pathology. This hypothesis is based on a high prevalence of Human Adenovirus (HAdV) 41F in affected children, together with metagenomic evidence of adeno-associated virus (Adeno-associated viruses)-2, which is a putative trigger for an immune-mediated liver injury. Roles for superantigen-mediated pathology have also been explored, with a focus on the potential contribution of SARS-CoV-2 infection. Affected children also had a high frequency of the MHC allele HLA-DRB1*04:01, supporting an immunological predisposition, and may have been vulnerable to viral coinfections due to disruption in normal patterns of exposure and immunity as a result of population lockdowns during the COVID-19 pandemic. We discuss areas of ongoing uncertainty, and highlight the need for ongoing scrutiny to inform clinical and public health interventions for this outbreak and for others that may evolve in future.
Ultrasound elastography is perhaps the most important breakthrough in the evolution of ultrasonography in the last 15 years. Since transient elastography was introduced, many other methods have been developed and became more and more widely available. The value of ultrasound elastography in staging a chronic liver disease has been established by numerous studies. There have been many studies that have shown that using liver elastography it is possible to predict the presence of the complications of cirrhosis: portal hypertension, presence of esophageal varices (and even their risk of bleeding) and hepatocellular carcinoma. It has been shown that liver elastography can predict the progression of liver fibrosis and also the survival (hepatic events - free) of the patients with chronic liver diseases. These are the real quests of the clinicians, this is the ultimate scope of any medical investigation - to predict the outcome of a patient and to help making therapeutic decisions. I brought together only a small amount of the data that has already been written on this subject to support my affirmation that liver ultrasound elastography is more than a tool for staging the liver disease, but it is also comparable to a crystal ball which in the hands of a skilled clinician can reveal the future of the patient and can help to improve this future.
Although nontoxigenic Vibrio cholerae usually stands in the shadow of the two serogroups (O1 and O139) that cause pandemic cholera, its role in human pathology is increasingly recognized and described in the literature. The habitat of these pathogens is brackish seawater or even freshwater, and the infections caused by them include contact with these waters or consumption of seafood originating in this habitat, which is constantly expanding because of global warming. This habitat extension is a typical example of climate change's impact on infectious diseases. Although nontoxigenic Vibrio cholerae strains are rarely capable of producing the classical cholera toxin, they possess many other virulence factors, can secrete various other toxins, and thus produce illnesses that are sometimes even severe or life-threatening, more frequently in immunocompromised patients. Vibriosis may manifest as gastrointestinal illnesses, wounds, skin or subcutaneous tissue infections, or septicemia. To establish the correct etiological diagnosis for these infections, a high index of suspicion must be maintained, as the diagnostic techniques require targeted investigations and specific collection and transportation of the samples. Empiric treatment recommendations are available, but owing to the increasing resistance of this pathogen, susceptibility testing is needed for every diagnosed case. We intend to raise awareness regarding these infections, as they tend to be more frequent than they were in the past and to appear in areas where they had not been recognized before.
Klebsiella pneumoniae, a member of the Enterobacterales Order, often colonises the gut and causes diverse infections, including bloodstream, urinary, and respiratory infections. The rise in carbapenem-resistant sFtrains, especially those producing enzymes like K. pneumoniae carbapenemase (KPC), New Delhi metallo-β-lactamase (NDM), Oxacillinase 48 (OXA48), or combinations (NDM+OXA48-like), poses a significant threat across Europe, notably in Romania. These strains spread rapidly via mobile genetic elements, complicating treatment. Methods: A retrospective study of multidrug-resistant (MDR) K. pneumoniae strains isolated from clinical samples collected at an infectious diseases hospital in Romania. Results: We analysed the evolution of carbapenemases and their combinations from 2010 to 2024, with the rising antibiotic consumption, particularly during the COVID-19 pandemic. The prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) rose from 4.9% in 2010 to 41.6% in 2024. There was an overall antibiotic use increase, especially colistin (186%) between 2019–2024. Additionally, we examined the dynamics of antibiotic susceptibility that decreased in 2023–2024 and found that susceptibility of NDM+OXA48-like isolates to colistin was 16.5% and to cefiderocol 58.5%. Conclusions: The rising prevalence of K. pneumoniae strains with complex resistance mechanisms, coupled with a significant reduction in available treatment options, demands a fundamental paradigm shift in the management of these infections.
Background and Aims: Chronic hepatitis delta represents a major global health burden. Clinical features of hepatitis D virus (HDV) infection vary largely between different regions worldwide. Treatment approaches are dependent on the approval status of distinct drugs and financial resources.Methods: The Hepatitis Delta International Network (HDIN) registry involves researchers from all continents (Wranke, Liver International 2018). We here report long‐term follow‐up data of 648 hepatitis D patients recruited by 14 centres in 11 countries. Liver‐related clinical endpoints were defined as hepatic decompensation (ascites, encephalopathy and variceal bleeding), liver transplantation, hepatocellular carcinoma or liver‐related death.Results: Patient data were available from all continents but Africa: 22% from Eastern Mediterranean, 32% from Eastern Europe and Central Asia, 13% from Central and Southern Europe, 14% from South Asia (mainly Pakistan) and 19% from South America (mainly Brazil). The mean follow‐up was 6.4 (.6–28) years. During follow‐up, 195 patients (32%) developed a liver‐related clinical event after 3.5 (±3.3) years. Liver cirrhosis at baseline and a detectable HDV RNA test during follow‐up were associated with a worse clinical outcome in multivariate regression analysis while patients receiving interferon alfa‐based therapies developed clinical endpoints less frequently. Patients from South Asia developed endpoints earlier and had the highest mortality.Conclusions: The HDIN registry confirms the severity of hepatitis D and provides further evidence for HDV viraemia as a main risk factor for disease progression. Hepatitis D seems to take a particularly severe course in patients born in Pakistan. There is an urgent need to extend access to antiviral therapies and to provide appropriate education about HDV infection.