OBJECTIVES: To investigate the impact of hepatitis B virus (HBV) infection on oral microbiota and metabolites in patients with metabolic dysfunction-associated fatty liver disease (MAFLD) and the underlying mechanisms. METHODS: This prospective study was conducted in 47 MAFLD patients complicated with chronic hepatitis B (CHB) and 48 MAFLD patients without CHB enrolled from November, 2023 to January, 2024. Fasting tongue coating samples were collected from the patients for analyzing microbial community structures and metabolites using high-throughput 16S rDNA sequencing and non-targeted metabolomics techniques, and their associations with clinical indicators and biological pathways were explored using correlation analysis and functional annotation. RESULTS: The levels of fasting blood glucose, total cholesterol (TC), gamma-glutamyl transferase (GGT), and severity of fatty liver were all significantly lower in MAFLD+CHB group than in MAFLD group. Microbiota analysis showed that the abundances of Patescibacteria (at the phylum level), Hydrogenophaga, and Absconditabacteriales (at the genus level) were significantly increased, while the abundance of Megasphaera was decreased in MAFLD+CHB group. The differential microbiota were significantly correlated with TC, GGT and low-density lipoprotein (r=-0.68‒0.75). Metabolomics analysis revealed that 469 metabolites (including lipids and amino acids) were upregulated and 2306 (including organic oxygen-containing compounds and phenylpropanoids) were downregulated in MAFLD+CHB group, for which KEGG enrichment analysis suggested abnormal activation of the linoleic acid metabolism and glycerophospholipid metabolism pathways. Correlation analysis between microbiota and metabolites indicated that Patescibacteria and Megasphaera, which were positively correlated with lipid metabolites and negatively with fatty acid metabolites, respectively, jointly affected glycolipid metabolism and oxidative stress pathways. CONCLUSIONS Compared to patients with MAFLD alone, MAFLD patients with concurrent chronic HBV infection showed lower levels in some lipid metabolism indicators and the degree of hepatic steatosis, accompanied by alterations in oral microbiota structure and metabolic profiles. The precise mechanisms involved require further investigation to be fully elucidated.
Humans ; Lipid Metabolism ; Prospective Studies ; Microbiota ; Hepatitis B, Chronic/microbiology* ; Male ; Female ; Adult ; Fatty Liver/microbiology* ; Middle Aged ; Mouth/microbiology* ; Metabolomics

Acute Disease ; Aged ; Anti-Bacterial Agents/therapeutic use* ; Bacteremia/microbiology* ; Female ; Hepatitis B, Chronic/complications* ; Hepatitis C, Chronic/complications* ; Humans ; Hypersplenism/complications* ; Liver Cirrhosis/complications* ; Meningococcal Infections/microbiology* ; Neisseria meningitidis/isolation & purification* ; Peritonitis/microbiology*

Adult ; Aged ; Bacterial Infections ; diagnosis ; immunology ; Female ; Hepatitis B, Chronic ; diagnosis ; immunology ; microbiology ; Humans ; Male ; Middle Aged ; Prognosis ; T-Lymphocyte Subsets ; immunology ; Young Adult

Aged ; Bacterial Infections ; drug therapy ; microbiology ; Drug Resistance, Bacterial ; Escherichia coli ; drug effects ; isolation & purification ; Female ; Hepatitis B, Chronic ; complications ; Hepatitis C, Chronic ; complications ; Humans ; Klebsiella pneumoniae ; drug effects ; isolation & purification ; Male ; Microbial Sensitivity Tests ; Middle Aged ; Peritonitis ; drug therapy ; microbiology

We report a case of acute fatal exacerbation of chronic hepatitis B in a 50-year-old man with multiple myeloma being treated with thalidomide. The patient had a medical history of chronic hepatitis B and was diagnosed with stage IIIA multiple myeloma. He suffered two episodes of transient transaminitis of unknown origin after successive autologous stem cell transplantations. Spontaneous resolutions of the transaminitis were observed without special management. At that time, PCR of hepatitis B virus (HBV) were all-negative. After 5-months' administration of thalidomide for the second relapse of the multiple myeloma, he suddenly experienced dizziness and jaundice. The level of HBV DNA was 1, 641 pg/mL and the serologic tests for other viruses were negative. Despite conventional supportive care, he expired due to septic shock caused by Klebsiella pneumonia. Based on the stable disease status of the multiple myeloma and exclusion of other hepatotoxic agents, it was assumed that the exacerbation of the hepatitis B virus during the thalidomide therapy preceded the bacterial sepsis. With the increased use of thalidomide in cancer treatment, cautious monitoring of the viral burden should be performed in patients with chronic hepatitis B.
Angiogenesis Inhibitors/administration & dosage/*adverse effects ; Hepatitis B, Chronic/*etiology ; Humans ; Klebsiella Infections/complications ; Male ; Middle Aged ; Multiple Myeloma/*drug therapy ; Shock, Septic/microbiology ; Thalidomide/administration & dosage/*adverse effects