Hepatitis B virus (HBV) genotype C is common in East Asia and is associated with poor outcomes, particularly liver cirrhosis and hepatocellular carcinoma (HCC). Clinically, genotype C infection is generally associated with persistent viral replication, later HBeAg seroconversion, more active hepatic inflammation, and an increased risk of HCC. Current evidence suggests that these features are driven by several key molecular events, including the A1762T/G1764A double mutation in the basal core promoter, the G1896A mutation in the precore region, abnormal hepatitis B virus X protein function, and viral integration. Together, these changes may reshape viral transcription, antigen expression, host immune interactions, and oncogenic signaling, thereby contributing to disease progression and hepatocarcinogenesis. Other factors, such as epigenetic changes, dysregulated DNA damage responses, impaired tumor protein p53 function, and disrupted autophagy, may also be involved, although their exact roles remain unclear. Notably, even after effective viral suppression with potent nucleos(t)ide analogs, patients with genotype C may still have a relatively high residual risk of HCC. This review summarizes the molecular virological features, pathogenic mechanisms, immune dysregulation, and clinical significance of HBV genotype C, and discusses the potential value of genotype information in risk stratification, long-term surveillance, and clinical assessment of chronic hepatitis B.

Observational studies indicate frequent associations between systemic lupus erythematosus (SLE) and various hematologic disorders, yet causal inferences are limited by confounding and reverse causality. We therefore applied a bidirectional Mendelian randomization (MR) design to assess potential genetic causal associations of SLE with specific hematologic conditions.

We used European-ancestry GWAS summary statistics for SLE (5,201 cases, 9,066 controls) and five hematologic outcomes (vitamin B12 deficiency anemia (B12DA), myelodysplastic syndrome (MDS), immune thrombocytopenia (ITP), agranulocytosis (AGC), iron deficiency anemia (IDA)) from FinnGen. The primary analysis used inverse-variance weighting, supplemented by MR-Egger and weighted median methods, with comprehensive sensitivity analyses, including heterogeneity tests, pleiotropy assessment, and leave-one-out analysis.

Bidirectional MR analysis revealed that genetically predicted SLE increased the risk of B12DA (odds ratio (OR) = 1.08, P < 0.001), and genetically predicted B12DA was associated with an increased risk of SLE (OR = 2.22, P = 1.6 × 10−29). The MDS → SLE association was nominally significant (P = 0.023) but did not survive Bonferroni correction (P < 0.005) and was inconsistent across MR methods. No significant genetic associations were found between SLE and ITP, AGC, or IDA in either direction (all P > 0.005).

This bidirectional MR study provides genetic evidence that SLE increases the risk of B12DA, whereas the reverse direction (B12DA → SLE) should be interpreted cautiously because it was based on only five instruments and was not supported by the Steiger directionality test. No robust genetic associations were found for ITP, AGC, IDA, or MDS. Clinically, monitoring B12DA in SLE patients may be warranted, although screening recommendations await prospective validation.

Randomized controlled trials (RCTs) have been conducted to evaluate treatment efficacy for metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis. This study aimed to compare the effectiveness and safety of 11 promising targets among adults with MASLD.

PubMed, Web of Science, the Cochrane Central Register of Controlled Trials, Scopus, and Embase were searched from inception to November 20, 2024. The primary outcomes were fibrosis improvement ≥1 stage without worsening of steatohepatitis and steatohepatitis resolution without worsening of fibrosis. Additional outcomes included reductions in liver fat content, liver enzymes, metabolic profiles, and selected safety outcomes. The surface under the cumulative ranking curve (SUCRA) was used to rank efficacy.

Of 11,584 articles screened, 44 eligible RCTs (11,410 participants, 33 medications) were included. For fibrosis improvement, d-(R)-pioglitazone (SUCRA: 79.3) and fibroblast growth factor (FGF) 21 analogs (SUCRA: 71.9) ranked higher. For steatohepatitis resolution, glucagon-like peptide-1 (GLP-1)/glucose-dependent insulinotropic polypeptide (GIP) dual receptor agonists (RAs) (SUCRA: 91.7) ranked higher. Co-agonists of GLP-1/GIP/GCG and GLP-1/GCG receptors ranked higher for relative and absolute changes in liver fat content, respectively. For liver enzymes and glucose improvement, the combination of a GLP-1 RA and an acetyl-coenzyme A carboxylase inhibitor ranked higher. GLP-1 RAs, peroxisome proliferator-activated RAs, and FGF21 analogs showed favorable effects on lipid profile improvement.

Incretin-based co-agonists and FGF21 analogs showed favorable profiles across key endpoints, while d-(R)-pioglitazone and GLP-1/GIP dual RAs ranked higher for fibrosis improvement and steatohepatitis resolution, respectively. SUCRA rankings should be interpreted in conjunction with effect sizes, uncertainty, and available safety data.

The huge burden of type 1 diabetes mellitus (T1DM) has been a source of concern globally since the Industrial Revolution in the 18th–19th centuries. To this end, studies have shown that certain environmental changes that accompanied the Revolution may have increased the risk and burden of the disease in genetically predisposed individuals. However, documented studies that synthesize these environmental triggers are scarce. As a result, the current study was conceived to synthesize the environmental triggers of T1DM to boost public awareness. Relevant information was retrieved from reputable academic databases; namely, Scopus, PubMed, SpringerLink, and Embase. The results showed that chemical exposure, viral infection, gut microbiome disruption, vitamin and mineral deficiencies, inadequate or exclusive breastfeeding, as well as early exposure to infant feeding formulas could increase the risk and burden of T1DM in genetically predisposed individuals. As a consequence, these triggers could compromise the expression of certain genes involved in insulin synthesis and immune function, such as the human leukocyte antigen (HLA), insulin (INS), cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), and protein tyrosine phosphatase non-receptor type 22 (PTPN22) genes. This would result in a dysfunctional immune system in which immune cells, such as T-cells and B-cells and molecules, such as cytokines would attack self-tissues, thus causing autoimmunity of the pancreatic beta cells. Environmental triggers could also induce the T1DM pathophysiology by modifying the epigenome of the mentioned genes. Furthermore, some epigenetic changes could be reversed, which would infer that treatment procedures that would include the pathophysiology of the environmental triggers could be more effective.

Emerging evidence suggests that RNA-binding motif (RBM) proteins are involved in hepatocarcinogenesis and act either as oncogenes or tumor suppressors. The objective of this study was to investigate the role of RBM34, an RBM protein, in hepatocellular carcinoma (HCC).

We first examined the expression of RBM34 across cancers. The correlation of RBM34 with clinicopathological features and the prognostic value of RBM34 for HCC was then investigated. Functional enrichment analysis of RBM34-related differentially expressed genes (DEGs) was performed to explore its biological function. RNA sequencing (RNA-seq) was applied to identify downstream genes and pathways affected upon RBM34 knockout. The correlation of RBM34 with immune characteristics was also analyzed. The oncogenic function of RBM34 was examined in in vitro and in vivo experiments.

RBM34 was highly expressed in hepatocellular carcinoma and correlated with poor clinicopathological features and prognosis. RBM34 was positively associated with tumor immune cell infiltration, biomarkers of immune cells, and immune checkpoint expression. A positive correlation was also observed between RBM34, T cell exhaustion, and regulatory T cell marker genes. Knockout of RBM34 significantly inhibited cell proliferation, migration, and xenograft tumor growth, and sensitized HCC cells to sorafenib treatment. RBM34 inhibition reduced FGFR2 expression and affected PI3K-AKT pathway activation in HCC cells.

Our study suggests that RBM34 may serve as a new prognostic marker and therapeutic target of HCC.

Naringenin is an anti-inflammatory flavonoid that has been studied in chronic liver disease. The mechanism specific to its antifibrosis activity needs further investigation This study was to focused on the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) pathway in hepatic stellate cells and clarified the antifibrosis mechanism of naringenin.

The relationship between the cGAS-stimulator of interferon genes (STING) pathway and liver fibrosis was analyzed using the Gene Expression Omnibus database. Histopathology, immunohistochemistry, fluorescence staining, Western blotting and polymerase chain reaction were performed to assess gene and protein expression levels associated with the cGAS pathway in clinical liver tissue samples and mouse livers. Molecular docking was performed to evaluate the relationship between naringenin and cGAS, and western blotting was performed to study the expression of inflammatory factors downstream of cGAS in vitro.

Clinical database analyses showed that the cGAS-STING pathway is involved in the occurrence of chronic liver disease. Naringenin ameliorated liver injury and liver fibrosis, decreased collagen deposition and cGAS expression, and inhibited inflammation in carbon tetrachloride (CCl4)-treated mice. Molecular docking found that cGAS may be a direct target of naringenin. Consistent with the in vivo results, we verified the inhibitory effect of naringenin on activated hepatic stellate cells (HSCs). By using the cGAS-specific agonist double-stranded (ds)DNA, we showed that naringenin attenuated the activation of cGAS and its inflammatory factors affected by dsDNA. We verified that naringenin inhibited the cGAS-STING pathway, thereby reducing the secretion of inflammatory factors by HSCs to ameliorate liver fibrosis.

Interrupting the cGAS-STING pathway helped reverse the fibrosis process. Naringenin has potential as an antihepatic fibrosis drug.