South Africa (SA) bears a significant burden of hepatitis B virus (HBV) infection, with a significant prevalence of hepatitis B surface antigen (HBsAg) among pregnant women. In response, the National Department of Health has recommended targeted birth-dose vaccination for infants born to HBsAg-positive mothers. While we commend the move towards antenatal HBsAg screening to identify infected pregnant women, we reiterate that a universal HBV birth-dose vaccination strategy would be a simpler, more equitable and more effective approach to preventing vertical transmission and reducing the overall HBV burden in SA.

Hepatitis B virus (HBV) infections cause chronic liver disease, resulting in about one million deaths per year, and there is currently no cure. Recent work has shown that a class of small molecules called capsid assembly modulators (CAMs) is promising for treating HBV. CAMs bind to HBV capsid protein subunits and alter their assembly, leading to non-functional and malformed structures rather than functional, closed shells. However, the mechanisms by which CAMs alter capsid assembly pathways remain unclear. Here, we extend a recently-developed kinetic Monte Carlo (KMC) model for HBV capsid assembly to simulate how CAMs affect assembly. In the model, CAMs alter assembly by preferentially binding to interfaces between certain quasi-equivalent subunit conformations. Simulations of the model reproduce experimental assembly product distributions. By analyzing assembly trajectories, we clarify the roles of thermodynamics and kinetics in determining assembly products, identify assembly mechanisms, and predict the key intermediates that lead to either capsids or malformed structures. Our findings enhance our fundamental understanding of capsid assembly, help advance the development of CAMs as a treatment for HBV and, more broadly, inform efforts to direct self-assembly pathways toward specific products.

Hemochromatosis (HC) is a disorder of iron metabolism characterized by excessive iron deposition in the body due to genetic mutations or secondary factors, leading to organ damage and dysfunction, particularly in the liver, heart, and pancreas. This disease is relatively rare in China, and cases of hemochromatosis occurring on the basis of post-hepatitis B‑related cirrhosis and subsequently inducing liver failure are even rarer. In October 2022, Guangdong Provincial Hospital of Traditional Chinese Medicine Hainan Hospital admitted a middle‑aged male patient with post-hepatitis B cirrhosis complicated by hemochromatosis, who subsequently developed acute-on-chronic liver failure (ACLF). The patient experienced a sudden and severe deterioration in liver function on the background of long-standing hepatitis B-related cirrhosis, meeting the diagnostic criteria for ACLF. Notably, liver failure occurred despite effective suppression of hepatitis B virus DNA replication, suggesting that non-viral factors contributed to the pathogenesis of liver failure. The diagnosis of hepatic hemochromatosis was ultimately confirmed by liver biopsy. Based on this case and a review of the literature, we propose that in patients with chronic liver disease, especially those presenting with unexplained acute deterioration of liver function or markedly elevated serum ferritin levels, hemochromatosis should be included in the routine differential diagnosis.

Semaglutide is a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1 RA), primarily used for the treatment of type 2 diabetes mellitus and obesity. Common adverse drug reactions (ADRs) include nausea, vomiting, diarrhea, abdominal pain, and constipation, whereas liver function-related ADRs are relatively rare. We report a rare and severe case of semaglutide-induced acute-on-chronic liver failure (ACLF) in a 47-year-old male patient who was successfully treated. The patient was admitted to the Department of Infectious Disease at the Second Xiangya Hospital of Central South University on December 1, 2023. He had a history of chronic hepatitis B and had discontinued antiviral therapy for more than two years without medical supervision. Due to weight loss requirements, he initiated subcutaneous semaglutide therapy. Approximately three months after treatment initiation, he developed severe liver dysfunction, which rapidly progressed to profound jaundice, coagulopathy, and hepatic encephalopathy. Drug-induced liver injury (DILI) was considered the primary precipitating factor of liver failure, and the final diagnosis was ACLF. Following confirmation of the diagnosis, semaglutide was discontinued, and comprehensive management, including hepatoprotective therapy, artificial liver support, plasma exchange, and liver transplantation, was implemented. The patient's clinical symptoms and liver function parameters improved significantly. This report describes the successful management of semaglutide-induced ACLF and reviews the relevant literature. For individuals with underlying chronic liver disease (e.g., chronic viral hepatitis), thorough baseline liver assessment should be performed prior to initiating semaglutide or similar agents. Close monitoring during treatment is essential to identify potential severe drug-induced liver injury at an early stage.

Viral hepatitis is one of the infectious diseases with an overall increasing mortality rate. The global burden of acute viral hepatitis remains substantial, with hepatitis A, B, C, D, and E responsible for millions of new cases annually and significant morbidity, especially in resource-limited settings and among travelers to endemic regions. People living with chronic viral hepatitis, especially with advanced liver disease, may face specific health risks and management challenges during travel, which makes preparing for travel especially important. Travel-related gastroenteritis or febrile syndromes can lead to more severe clinical outcomes due to limited hepatic reserve. Newly acquired hepatitis A and E significantly increase the risk of liver failure and mortality in patients with chronic liver disease. This review emphasizes the critical importance of checking the immunization status of patients with chronic viral hepatitis before travel, managing antiviral medications, assessing risk of complications, evaluating the health infrastructure of the destination country, and applying food and water safety precautions. Safe travel for patients with chronic viral hepatitis can be facilitated through an appropriate risk assessment and a personalized travel plan.

Sphingolipids regulate hepatic lipid homeostasis, cell survival, inflammation, and tissue repair. In the healthy liver, balanced de novo sphingolipid synthesis, salvage pathways, and sphingosine-1-phosphate (S1P)-related signals maintain metabolic flexibility, endothelial integrity, and immune quiescence. Dysregulation of sphingolipid metabolism drives the initiation and progression of chronic liver diseases. In metabolic dysfunction-associated steatohepatitis, the acyl chain length-specific remodeling of dihydroceramides and ceramides, together with increased neutral sphingomyelinase activity, triggers lipotoxic stress, abnormal anabolic signal transduction, and hepatic lobule inflammation. Liver fibrosis involves reprogramming of the hepatic stellate cell S1P receptor signaling from regenerative toward profibrotic pathways. In hepatocellular carcinoma, tumor cells utilize sphingolipid metabolism to promote angiogenesis, evade immune surveillance, and develop therapeutic resistance. Sphingolipid remodeling in viral hepatitis links viral persistence to distinct circulating lipid signatures that correlate with disease severity and prognosis. Importantly, multiple nodes in the sphingolipid network and their downstream effectors are emerging as therapeutic targets. Promising preclinical strategies include liver-targeted small interfering RNA against key biosynthetic enzymes, selective modulation of sphingolipid receptors, and nanoliposomal formulations of bioactive ceramides. To enable clinical translation, innovative approaches are being developed to overcome key challenges in delivery, specificity, and safety. Overall, this review integrates recent mechanistic insights, emphasizing that sphingolipids act as central regulators of liver pathophysiology and are also important biomarkers and therapeutic targets in chronic liver diseases.