Infection by dengue virus is common in tropical countries. Hepatic involvement in dengue can range from asymptomatic elevation of transaminases to life-threatening acute liver failure (ALF). Dengue-related ALF (DALF) is responsible for significant morbidity and mortality, especially in Southeast Asia. However, there is a scarcity of literature on DALF, necessitating a thorough examination of its clinical determinants and management strategies. All relevant studies related to DALF were reviewed until December 2023. Case reports, case series and studies reporting ALF in dengue infection were included. Demographics, clinical profiles, management and outcomes of DALF cases were analyzed, which revealed a predominance of DALF incidence in pediatric patients (1.1% to 15.8%) and an upward trend over the years, particularly in India. The proportion of ALF cases attributable to dengue was also higher among pediatric ALF patients (6.7% to 34.3%). Age ≤ 40 years, persistent nausea, vomiting and elevated serum bilirubin and alkaline phosphatase (ALP) with aspartate aminotransferase (AST) > 1000 IU/mL within the first five days of illness, more than 10% of atypical lymphocytes in peripheral blood, platelet count of < 50,000/cu·mm, severe hepatitis at presentation and baseline model for end-stage liver disease (MELD) > 15 were the risk factors for the development of DALF. Histopathological features of DALF included multi-lobular hepatic necrosis, steatosis and occasional cholestasis. Mortality in DALF ranged from 0% to 80%; admission pH and lactate strongly predicted mortality, while mortality was found to be significantly higher in patients with cirrhosis. N-Acetyl cysteine (NAC) has been used as a treatment modality with varying results. There is limited evidence regarding the use of extra-corporeal support systems, while candidate selection for liver transplantation (LT) in DALF remains poorly defined.

An increase in severe acute hepatitis of unknown etiology was first reported in the United Kingdom in April 2022. Following this report, the Public Health Agency of Canada connected with three paediatric liver transplant centres across Canada to determine if an increase in liver transplants was noted. Data demonstrated no observable increase in the number of transplants conducted in 2022. These data in conjunction with a federal, provincial, territorial investigation provided insight into the situation in Canada.

Hepatitis E virus (HEV) is a small non-enveloped virus that is transmitted via the fecal-oral route. It is a highly common cause of acute hepatitis, particularly in low to middle income regions of Asia, Africa, and Central America. Most cases are self-limited, and symptomatic patients usually present with acute icteric hepatitis. A subset of patients including pregnant women, older men, those with pre-existing liver disease and immunocompromised patients however, may develop severe disease and hepatic failure. Immunocompromised patients are also at risk for chronic infection, and their immunosuppression should be decreased in order to facilitate viral clearance. HEV can also present with a variety of extra-intestinal manifestations including neurological, renal, hematological, and pancreatic derangements. The gold standard of diagnosis is HEV ribonucleic acid detection via nucleic acid amplification testing. Currently, there are no approved treatments for Hepatitis E, though ribavirin is the most commonly used agent to reduce viral load. Studies assessing the safety and efficacy of other antiviral agents for HEV are currently underway. HEV vaccination has been approved in China, and is currently being investigated in other regions as well. This review article aims to discuss the epidemiology, pathogenesis, presentation, diagnosis, complications, and treatment of Hepatitis E infection.

BACKGROUND: An important but rare adverse effect of vaccines is their association with autoimmune events, including hepatitis and aplastic anemia (AA). In this paper, we report a case of hepatitis followed by AA that occurred after the COVID-19 vaccine was administered.
METHODS: This paper focuses on a 30-year-old female who presented with acute hepatitis three weeks after receiving the second dose of the coronavirus Pfizer/BioNTech vaccine. After an extensive diagnostic evaluation was conducted that did not discover a specific cause, the Pfizer/BioNTech vaccine was suspected and the patient was treated with corticosteroids. One week after the onset of a liver disorder, the patient presented with gum bleeding and pancytopenia, and the diagnosis of AA was established via laboratory testing and bone marrow biopsy. After the diagnosis, the patient received immunosuppressive therapy using anti-lymphocyte serum (ATGAM) and CYCLOSPORINE A with progressive improvements in cytopenia. The important issue is whether AA is related to acute hepatitis or the coronavirus vaccine.
CONCLUSIONS: Clinicians should be aware of the risk of both the possibility of acute hepatitis, AA, or both after receiving the COVID-19 vaccination. It is very hard to distinguish the cause of AA between vaccine- and hepatitis-related AA. Predicting who develops hepatic or myelo-complications after vaccination is difficult.

Drug-induced liver injury (DILI) remains a challenge in clinical practice and is still a diagnosis of exclusion. Although it has a low incidence amongst the general population, DILI accounts for most cases of acute liver failure with a fatality rate of up to 50%. While multiple mechanisms of DILI have been postulated, there is no clear causal relationship between drugs, risk factors and mechanisms of DILI. Current best practice relies on a combination of high clinical suspicion, thorough clinical history of risk factors and timeline, and extensive hepatological investigations as supported by the international Roussel Uclaf Causality Assessment Method criteria, the latter considered a key diagnostic algorithm for DILI. This review focuses on DILI classification, risk factors, clinical evaluation, future biomarkers and management, with the aim of facilitating physicians to correctly identify DILI early in presentation.

Severe cases of acute hepatitis have been reported all around the world since 5 April 2022. Common viral hepatitis agents (HAV, HBV, HCV, HDV, and HEV) were ruled out by laboratory investigations, impelling the term \"acute non-A-E hepatitis\". Common manifestations consist of abdominal pain, jaundice, and vomiting. A highly elevated level of liver enzymes was a remarkable laboratory finding among the patients. Currently, there is no clear etiology and thus treatment for the condition. Adenovirus serotype 41 (ad-41) was detected in most of the patients even though there is no elucidated link between Adenovirus and acute hepatitis. Other viral agents such as SARS-CoV-2 tested positive in a few cases. Treatment strategies depend on the severity, complications, and sequela of acute hepatitis and can vary widely from supportive therapy to liver transplantation. As of 8 July 2022, 1010 probable cases were reported from 35 countries. More than half were from the European region and were mostly children under the age of 6 years. Among different hypotheses about the etiology of severe acute non-A-E hepatitis, adenovirus-41 is of great importance but further assessments are needed to prove any definite link between ad-41 and severe acute hepatitis.

In October 2021, a case of acute hepatic failure without any known cause was identified in the United States of America. Upon further investigation, other children aged 1-6 years were reported to have the same liver failure, and some of them were positive for adenovirus 41 type F. On 21 April 2022, the Centers for Disease Control and Prevention (CDC) released an alert after 74 cases were identified in United Kingdom (UK) between 5 and 8 April in children below 10 years of age, some of whom were also found to be positive for SARS-CoV-2. All the patients showed symptoms such as vomiting, diarrhea, jaundice, and abdominal pain. The patients\' liver enzymes were remarkably increased. A total of 650 cases had been reported from 33 countries as of 27 May 2022, among which 222 cases were reported in the UK alone. No connection with SARS-CoV-2 or its vaccine has been found so far. However, the suspected cause is adenovirus, including its genomic variations, because its pathogenesis and laboratory investigations have been positively linked. Until further evidence emerges, hygiene precautions could be helpful to prevent its spread.

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.

Of 350 million people worldwide are chronically infected with hepatitis B virus (HBV) and are at risk of developing cirrhosis and hepatocellular carcinoma (HCC) later in life. HBV is the most diverse DNA virus, and its genome is composed of four open reading frames: Presurface antigen/surface antigen gene (preS/S), precore/core gene (preC/C), polymerase gene (P), and the X gene (X). HBV produces quasispecies naturally or in response to antiviral agents because of the absence of proofreading activity amid reverse transcription and a high replication rate. The virus has 10 genotypes (A to J) with different geographical distributions. There are various HBV mutations in the HBV genome, including preC/C mutations, preS/S mutations, P gene mutations, and X gene mutations. The core promoter region plays a vital part in the replication, morphogenesis and pathogenesis of the virus. The precore region also plays a crucial role in viral replication. Both core promoter and precore mutations rescue the virus from host immune surveillance and result in the formation of mutated strains that may have altered pathogenicity. preC/C mutations are associated with liver disease progression. Precore mutations stop hepatitis B e antigen (HBeAg) production and basal core promoter mutations downregulate HBeAg production. Mutations in the basal core promoter are also associated with increased HBV replication and an increased incidence of advanced liver diseases such as cirrhosis and HCC. The emergence of antiviral-resistant mutations is the main reason for treatment failure. This review focuses mainly on preC/C promoter mutations and their correlation with genotypes and liver disease severity. Thorough perception and knowledge of HBV genetic variety and mutants could be vital to discover techniques for the prognosis and control of HBV infection.

Novel coronavirus disease 2019 (COVID-19) is a single-stranded RNA virus identified for the first time in Wuhan, China, and it unfurls quickly worldwide. The corona virus 2019 is a systemic disease which develops a prothrombotic environment, and has an extensive spectrum of clinical presentations in the gastrointestinal and hepatobiliary systems. Ischemic hepatitis (hypoxic hepatitis) is one potential mechanism behind lessened perfusion of the liver. The portal and mesenteric vein thrombosis are extremely rare complications and unusual main manifestations of COVID-19. We report the case of a patient presented acute hepatitis with portal and mesenteric vein thrombosis revealing a SARS-CoV-2 infection. In addition, we discuss the most characteristic elements of the Impact of COVID-19 on liver Injury, and the mechanisms of this damage and the formation of thrombus in portal and mesenteric vein.