Toxic epidermal necrolysis (TEN) is a rare but serious immune-mediated life-threatening skin and mucous membrane reaction that is mainly caused by drugs, infections, vaccines, and malignant tumors. A 74-year-old woman presented with a moderate fever of unknown cause, which was relieved after 2 days, but with weakness and decreased appetite. Red maculopapules appeared successively on the neck, trunk, and limbs, expanding gradually, forming herpes and fusion, containing a yellow turbidous liquid and rupturing to reveal a bright red erosive surface spreading around the eyes and mouth. The affected body surface area was >90%. The severity of illness score for toxic epidermal necrolysis was 2 points. The drug eruption area and severity index score was 77. She was diagnosed with TEN caused by hepatitis A virus and treated with 160 mg/day methylprednisolone, 300 mg/day cyclosporine, and 20 g/day gammaglobulin. Her skin showed improvements after 3 days of treatment and returned to nearly normal after 1 month, and liver function was completely normal after 2 months.

Hepatitis A and hepatitis E are relatively common causes of liver disease. Both viruses are mainly transmitted through the faecal-oral route and, consequently, most outbreaks occur in countries with poor sanitation. An important role of the immune response as the driver of liver injury is also shared by the two pathogens. For both the hepatitis A (HAV) and hepatitis E (HEV) viruses, the clinical manifestations of infection mainly consist of an acute disease with mild liver injury, which results in clinical and laboratory alterations that are self-limiting in most cases. However, severe acute disease or chronic, long-lasting manifestations may occur in vulnerable patients, such as pregnant women, immunocompromised individuals or those with pre-existing liver disease. Specifically, HAV infection rarely results in fulminant hepatitis, prolonged cholestasis, relapsing hepatitis and possibly autoimmune hepatitis triggered by the viral infection. Less common manifestations of HEV include extrahepatic disease, acute liver failure and chronic HEV infection with persistent viraemia. In this paper, we conduct a non-systematic review of the available literature to provide a comprehensive understanding of the state of the art. Treatment mainly consists of supportive measures, while the available evidence for aetiological treatment and additional agents in severe disease is limited in quantity and quality. However, several therapeutic approaches have been attempted: for HAV infection, corticosteroid therapy has shown outcome improvement, and molecules, such as AZD 1480, zinc chloride and heme oxygenase-1, have demonstrated a reduction in viral replication in vitro. As for HEV infection, therapeutic options mainly rely on the use of ribavirin, and some studies utilising pegylated interferon-alpha have shown conflicting results. While a vaccine for HAV is already available and has led to a significant reduction in the prevalence of the disease, several vaccines for HEV are currently being developed, with some already available in China, showing promising results.

Hepatitis A virus (HAV) has some life-threatening extrahepatic complications, such as acute acalculous cholecystitis (AAC). We present HAV-induced AAC in a young female, based on clinical, laboratory, and imaging findings, and conduct a literature review. The patient became irritable, which progressed to lethargy, as well as a significant decline in liver function, indicating acute liver failure (ALF). She was immediately managed in the intensive care unit with close airway and hemodynamic monitoring after being diagnosed with ALF (ICU). The patient\'s condition was improving, despite only close monitoring and supportive treatment with ursodeoxycholic acid (UDCA) and N-acetyl cysteine (NAC).

BACKGROUND: Acute acalculous cholecystitis (AAC) is inflammation of the gallbladder without evidence of calculi. Although rarely reported, its etiologies include hepatitis virus infection (e.g., hepatitis A virus, HAV) and adult-onset Still\'s disease (AOSD). There are no reports of HAV-associated AAC in an AOSD patient.
METHODS: Here we report a rare case of HAV infection-associated AAC in a 39-year-old woman who had a history of AOSD. The patient presented with an acute abdomen and hypotension. Elevated hepatobiliary enzymes and a thickened and distended gallbladder without gallstones on ultrasonography suggested AAC, but there were no signs of anemia nor thrombocytopenia. Serological screening revealed anti-HAV IgM antibodies. Steroid treatment did not alleviate her symptoms, and she was referred for laparoscopic cholecystectomy. The resected gallbladder was hydropic without perforation, and her clinical signs gradually improved after surgery.
CONCLUSIONS: AAC can be caused by HAV in AOSD patients. It is crucial to search for the underlying etiology for AAC, especially uncommon viral causes.

Vaccination has been confirmed to be the safest and, sometimes, the only tool of defense against threats from infectious diseases. The successful history of vaccination is evident in the control of serious viral infections, such as smallpox and polio. Viruses that infect human livers are known as hepatitis viruses and are classified into five major types from A to E, alphabetically. Although infection with hepatitis A virus (HAV) is known to be self-resolving after rest and symptomatic treatment, there were 7134 deaths from HAV worldwide in 2016. In 2019, hepatitis B virus (HBV) and hepatitis C virus (HCV) resulted in an estimated 820,000 and 290,000 deaths, respectively. Hepatitis delta virus (HDV) is a satellite virus that depends on HBV for producing its infectious particles in order to spread. The combination of HDV and HBV infection is considered the most severe form of chronic viral hepatitis. Hepatitis E virus (HEV) is another orally transmitted virus, common in low- and middle-income countries. In 2015, it caused 44,000 deaths worldwide. Safe and effective vaccines are already available to prevent hepatitis A and B. Here, we review the recent advances in protective vaccines against the five major hepatitis viruses.

Hepatitis A is a common form of viral hepatitis. It is usually transmitted through the ingestion of contaminated food and water. This systematic review was carried out to summarise the overall prevalence of Hepatitis A virus (HAV) in different water matrices: untreated and treated wastewater, surface water, groundwater, drinking water, and others (e.g., irrigation water and floodwater). The literature search was performed in four databases: PubMed, Web of Science, Global Index Medicus, and Excerpta Medica Database. Heterogeneity (I2) was assessed using the χ2 test on the Cochran Q statistic and H parameters. A total of 200 prevalence data from 144 articles were included in this meta-analysis. The overall prevalence of HAV in water matrices was 16.7% (95% CI: 13.4−20.3). The prevalence for individual matrix was as follows: 31.4% (95% CI: 23.0−40.4) untreated wastewater, 18.0% (95% CI: 9.5−28.2) treated wastewater, 15.0% (95% CI: 10.1−20.5) surface water, 2.3% (95% CI: 0.1−6.0) in groundwater, 0.3% (95% CI: 0.0−1.7) in drinking water, and 8.5% (95% CI: 3.1−15.6) in other matrices. The prevalence was higher in low-income economies (29.0%). Africa and Eastern Mediterranean were the regions with higher HAV prevalence values. This study showed a high heterogeneity (I2 > 75%) with a significant publication bias (p value Egger test < 0.001). The results of this review suggest that water matrices could be an important route of HAV transmission even in industrialized countries, despite the lower prevalence compared to less industrialized countries, and the availability of advanced water management systems. More effective water/wastewater treatment strategies are needed in developing countries to limit the environmental circulation of HAV.

UNASSIGNED: Although several reviews of economic evaluation (EE) studies on hepatitis A virus (HAV) vaccine exist, there remains a need to corroborate such data from time to time. This study aimed to systematically review the literature for reports on EE of HAV vaccination by type of population, characteristics of intervention and income level of the country.
UNASSIGNED: PubMed and Scopus were searched to identify relevant studies from inception up to May 2021 using topic-specific key words in various combinaiton. Full EE studies comparing HAV vaccination to no vaccine or immunoglobulin were included. The risk of bias was assessed by using the ECOBIAS checklist.
UNASSIGNED: Among the 1984 identified studies, 43 were found eligible. Of these, 27 were from high-income countries (HICs), 15 from middle-income countries (MICs), and one from low income country. Majority of the studies used Markov model and/or decision tree (n=26). Eight studies used a dynamic model. The discount rate, perspective and time horizon varied across the studies. Universal HAV vaccination without screening was cost-effective among children (14/16, 87.5%) and adolescents (1/5, 20%) but not in adults (0/4, 0%). Analysis by the level of income found that universal HAV vaccination among children without screening was cost-effective in 81.8 per cent of the studies conducted in MICs (9/11) as compared to 66.7 per cent in HICs (4/6). About one-third of the studies conducted among children found that screening and HAV vaccination were cost-effective compared to no vaccination.
UNASSIGNED: The finding of this review suggest that universal vaccination of children without screening was likely to be cost-effective, especially in MICs. Nevertheless, it should be noted that the methodology varied across studies. Several aspects should also be considered in transferring the EE results across jurisdictions.

Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are acute inflammatory skin adverse reactions characterized by epidermal exfoliation and multi-site mucositis and are considered medical emergencies. The risk factors for SJS/TEN include immune disorders, malignancy, and genetic susceptibility. In most cases, medication is considered to be the leading cause of TEN. In addition, several studies suggest that infections, such as the herpes simplex virus, human immunodeficiency virus (HIV), Mycoplasma pneumoniae, streptococcus, and meningococcus infections, can trigger the occurrence of SJS/TEN. In this rare case, we share our experience managing TEN in a hepatitis A virus infection with an acute-on-chronic liver failure patient. A 38-year-old man was infected with hepatitis A virus on the basis of liver cirrhosis and progressed to acute-on-chronic liver failure. As the infection progressed, the target-like skin lesions accompanied by mucosal involvement worsened. The condition of the patient progressively worsened with a severe generalized rash, bullae, and epidermal detachment accompanied by severe erosive mucosal lesions. His skin detachment area gradually involved 30% of the body surface area (BSA), and the disease progressed to TEN. The intravenous infusion of corticosteroids alleviated the patient\'s hypersensitivity, and the patient obtained lasting remission without severe adverse reactions and complications.

Medicinal plants have been used to treat different diseases throughout the human history namely in traditional medicine. Most of the plants mentioned in this review article belong among them, including those that are widely spread in the nature, counted frequently to be food and nutrition plants and producing pharmacologically important secondary metabolites. Triterpenoids represent an important group of plant secondary metabolites displaying emerging pharmacological importance. This review article sheds light on four selected triterpenoids, oleanolic, ursolic, betulinic and platanic acid, and on their amide derivatives as important natural or semisynthetic agents in cancer treatment, and, in part, in pathogenic microbe treatment. A literature search was made in the Web of Science for the given key words covering the required area of secondary plant metabolites and their amide derivatives. The most recently published findings on the biological activity of the selected triterpenoids, and on the structures and biological activity of their relevant amide derivatives have been summarized therein. Mainly anti-cancer effects, and, in part, antimicrobial and other effects of the four selected triterpenoids and their amide derivatives have also been reviewed. A comparison of the effects of the parent plant products and those of their amide derivatives has been made.

BACKGROUND: Hepatitis A virus infections are mostly asymptomatic or mildly symptomatic, and generally this disease has a benign course and resolves spontaneously. However, intrahepatic and rarer extrahepatic manifestations can complicate typical cases of acute hepatitis. Pleural effusion is an extremely rare extrahepatic entity with 20 cases reported in literature.
METHODS: We report herein a recent case of both pleural effusion and ascites accompanying hepatitis A infection in a 5-year-old middle eastern child, diagnosed using serological testing and imaging studies, who was treated with supportive management with full resolution after 2 weeks. In addition, we review available literature regarding hepatitis A virus associated with pleural effusion using PubMed and summarize all reported cases in a comprehensive table.
RESULTS: Literature contains 20 reported cases of serology-confirmed hepatitis A virus presenting with pleural effusion, most in the pediatric population with average age at presentation of 9 years 8 months. The majority of reported patients had right-sided pleural effusion (50%) or bilateral effusion (45%), while only 5% presented with pleural effusion on the left side. Hepatomegaly and ascites occurred concurrently in 80% and 70% respectively. Supportive treatment without invasive procedures (except one chylothorax case) yielded complete recovery in 95% of cases, while only one case progressed to fulminant liver failure followed by death.
CONCLUSIONS: Acute hepatitis A virus rarely presents with pleural effusion, usually following a benign course with spontaneous resolution in most patients. Pleural effusion does not change the prognosis or require any invasive treatment. Thus, further invasive procedures are not recommended and would only complicate this self-resolving benign condition.