Hepatocellular carcinoma (HCC) is a highly lethal malignancy associated with poor prognosis due to late-stage diagnosis and high recurrence rates. The MEX3 family genes has been implicated in various cancers; however, their roles in HCC remain largely unexplored. This study aims to systematically analyze the expression patterns, prognostic significance, and immune-related functions of MEX3A, MEX3B, MEX3C, and MEX3D in HCC using comprehensive bioinformatics approaches. We conducted a multi-level bioinformatics analysis to investigate the expression, prognostic significance, clinicopathological correlations, genetic alterations, immune associations, and functional mechanisms of MEX3 family members in HCC. Transcriptomic data from TCGA and GEO databases, along with experimental validation via qRT-PCR and Western blotting, were used to assess expression profiles. Kaplan-Meier, ROC curve, and Cox regression analyses were employed for prognostic evaluation. Co-expression, enrichment, and immune infiltration analyses further elucidated the functional and immunological relevance of MEX3 family genes. A prognostic model based on co-expressed genes was constructed and validated using LASSO and time-dependent ROC analyses. MEX3A, MEX3B, MEX3C, and MEX3D were significantly upregulated in HCC tissues compared to normal liver tissues (P < 0.05). ROC curve analysis demonstrated high diagnostic accuracy, particularly for MEX3A (AUC = 0.915). Kaplan-Meier survival analysis indicated that elevated MEX3A and MEX3C expression was associated with poorer overall survival (OS) and disease-specific survival (DSS) (P < 0.05). Mutation analysis revealed that MEX3A exhibited the highest alteration frequency (11%), primarily through gene amplifications. Immune infiltration analysis demonstrated significant correlations between MEX3 expression and multiple immune cell populations, including regulatory T cells (Tregs), cytotoxic T cells, and macrophages. Moreover, MEX3B, MEX3C, and MEX3D expression correlated with key immune checkpoint genes, including PDCD1, CD274, and CTLA4. Functional enrichment analysis revealed that MEX3 co-expressed genes were significantly involved in RNA metabolism, immune response regulation, and oncogenic signaling pathways. A 17-gene MEX3 co-expression-based prognostic model stratified patients into high- and low-risk groups with significantly different survival outcomes (AUC = 0.791 at 1 year). This study highlights the oncogenic potential of MEX3 family members in HCC and their associations with immune regulation. The findings suggest that MEX3 family genes could serve as potential biomarkers for HCC prognosis and immunotherapy responsiveness. Further experimental validation is warranted to elucidate the mechanistic roles of MEX3 family genes in HCC progression and immune evasion.

We assessed the impact of the COVID-19 pandemic on hepatocellular carcinoma (HCC) surveillance among individuals with HCV diagnosed with cirrhosis in British Columbia (BC), Canada. We used data from the British Columbia Hepatitis Testers Cohort (BC-HTC), including all individuals in the province tested for or diagnosed with HCV from 1 January 1990 to 31 December 2015, to assess HCC surveillance. To analyse the impact of the pandemic on HCC surveillance, we used pre-policy (January 2018 to February 2020) and post-policy (March to December 2020) periods. We conducted interrupted time series (ITS) analysis using a segmented linear regression model and included first-order autocorrelation terms. From January 2018 to December 2020, 6546 HCC screenings were performed among 3429 individuals with HCV and cirrhosis. The ITS model showed an immediate decrease in HCC screenings in March and April 2020, with an overall level change of -71 screenings [95% confidence interval (CI): -105.9, -18.9]. We observed a significant decrease in HCC surveillance among study participants, regardless of HCV treatment status and age group, with the sharpest decrease among untreated HCV patients. A recovery of HCC surveillance followed this decline, reflected in an increasing trend of 7.8 screenings (95% CI: 0.6, 13.5) per month during the post-policy period. There was no level or trend change in the number of individuals diagnosed with HCC. We observed a sharp decline in HCC surveillance among people living with HCV and cirrhosis in BC following the COVID-19 pandemic control measures. HCC screening returned to pre-pandemic levels by mid-2020.

The change in hepatocellular carcinoma (HCC) care continuum during the coronavirus disease 2019 (COVID-19) pandemic remains unknown at a national level in the United States. We sought to determine the impact of the pandemic on incident HCC cases, clinical characteristics, and treatment in the United States.

Using the National Cancer Database, we analyzed incident HCC cases from 2010 to 2020. The incidence rate was calculated using the population data for each year from the census bureau. Joinpoint regression analysis was applied for trend analysis, and a polynomial regression model estimated the number of projected HCC cases in 2020 according to the trend of rates from 2010 to 2019. The distribution of cancer stage and treatment modality were assessed.

The pandemic led to a significant reduction in reported HCC cases, from 19,597 in 2019 to 16,188 in 2020. The projected number of HCC for 2020 was 19,011, corresponding to a 14.8% reduction in 2020. Extent of reduction in the number of incident HCC cases relative to estimated cases remains consistent in racial and ethnic subgroups. Despite underdiagnosis of HCC in 2020, proportion of patients with early tumor stage (30.5% for Tumour, Node, Metastasis stage 1) and curative treatment receipt (9.1% for surgical resection, 13% for ablation, 4.2% for liver transplant) for HCC remained stable in the first year of the COVID-19 pandemic.

There was a significant reduction in HCC cases in 2020 compared to pre-COVID years. While tumor stage and proportion of patients receiving curative treatment remained stable, continued follow-up is needed to assess potential changes during subsequent years.

In late 2019, the world was shaken by the COVID-19 pandemic. Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection became one of the main causes of illness and hospitalization worldwide, especially in subjects with metabolic comorbidities such as obesity, diabetes, or liver disease. This scenario crosses with the metabolic liver disorders' "pandemic", caused by the exponential spreading of non-alcoholic fatty liver disease, which is now the most prevalent cause of chronic liver disease (CLD). The aim of this review is to analyze the key factors of the relationship between COVID-19 and the spectrum of fatty liver disorders (FLD), in terms of molecular mechanisms and clinical presentation which can predict a more severe course of the infection. In addition, this review will face the change in management of FLD during pandemics, with a central role of telemedicine, and the role of other interventions in preventing and treating severe infection in these subjects.

Early in the coronavirus disease 2019 (COVID-19) pandemic, there was a significant impact on routine medical care in the United States, including in fields of transplantation and oncology.

To analyze the impact and outcomes of early COVID-19 pandemic on liver transplantation (LT) for hepatocellular carcinoma (HCC) in the United States.

WHO declared COVID-19 as a pandemic on March 11, 2020. We retrospectively analyzed data from the United Network for Organ Sharing (UNOS) database regarding adult LT with confirmed HCC on explant in 2019 and 2020. We defined pre-COVID period from March 11 to September 11, 2019, and early-COVID period as from March 11 to September 11, 2020.

Overall, 23.5% fewer LT for HCC were performed during the COVID period (518 vs 675, P < 0.05). This decrease was most pronounced in the months of March-April 2020 with a rebound in numbers seen from May-July 2020. Among LT recipients for HCC, concurrent diagnosis of non-alcoholic steatohepatitis significantly increased (23 vs 16%) and alcoholic liver disease (ALD) significantly decreased (18 vs 22%) during the COVID period. Recipient age, gender, BMI, and MELD score were statistically similar between two groups, while waiting list time decreased during the COVID period (279 days vs 300 days, P = 0.041). Among pathological characteristics of HCC, vascular invasion was more prominent during COVID period (P < 0.01), while other features were the same. While the donor age and other characteristics remained same, the distance between donor and recipient hospitals was significantly increased (P < 0.01) and donor risk index was significantly higher (1.68 vs 1.59, P < 0.01) during COVID period. Among outcomes, 90-day overall and graft survival were the same, but 180-day overall and graft were significantly inferior during COVID period (94.7 vs 97.0%, P = 0.048). On multivariable Cox-hazard regression analysis, COVID period emerged as a significant risk factor of post-transplant mortality (Hazard ratio 1.85; 95%CI: 1.28-2.68, P = 0.001).

During COVID period, there was a significant decrease in LTs performed for HCC. While early postoperative outcomes of LT for HCC were same, the overall and graft survival of LTs for HCC after 180 days were significantly inferior.

Coronavirus disease 2019 (COVID-19) is primarily a respiratory disease with multi-organ involvement, including impaired liver function. It has been noticed that a significant proportion of COVID-19 patients have liver dysfunction, especially those with a more severe disease course. The coronavirus causes direct damage to the liver using the angiotensin-converting enzyme 2, a cell-surface receptor for cellular entry, that is expressed in the liver. According to previous research, liver enzyme abnormalities were observed in a considerable proportion of COVID-19 patients, and elevated liver transaminases were found in about 20% of these patients, alkaline phosphatase in 6.1%, and gamma-glutamyl transferase in 21.1%. COVID-19 might trigger a deterioration of liver function in patients with pre-existing chronic liver diseases (CLDs) and also in those without previous liver disorders. The majority of COVID-19 patients who develop liver injury are men, the elderly, and those with a higher body mass index. Compared to the general population, COVID-19 is associated with significant morbidity and mortality in patients with liver disease (cirrhosis and liver transplantation recipients). However, some studies indicate that CLDs have a lesser role in determining patient progression towards higher disease severity.

The global outbreak of COVID-19 possesses serious challenges and adverse impacts for patients with progression of chronic liver disease and has become a major threat to public health. COVID-19 patients have a high risk of lung injury and multiorgan dysfunction that remains a major challenge to hepatology. COVID-19 patients and those with liver injury exhibit clinical manifestations, including elevation in ALT, AST, GGT, bilirubin, TNF-α, and IL-6 and reduction in the levels of CD4 and CD8. Liver injury in COVID-19 patients is induced through multiple factors, including a direct attack of SARS-CoV-2 on liver hepatocytes, hypoxia reperfusion dysfunction, cytokine release syndrome, drug-induced hepatotoxicity caused by lopinavir and ritonavir, immune-mediated inflammation, renin-angiotensin system, and coagulopathy. Cellular and molecular mechanisms underlying liver dysfunction are not fully understood in severe COVID-19 attacks. High mortality and the development of chronic liver diseases such as cirrhosis, alcoholic liver disease, autoimmune hepatitis, nonalcoholic fatty liver disease, and hepatocellular carcinoma are also associated with patients with liver damage. COVID-19 patients with preexisting or developing liver disease should be managed. They often need hospitalization and medication, especially in conjunction with liver transplants. In the present review, we highlight the attack of SARS-CoV-2 on liver hepatocytes by exploring the cellular and molecular events underlying the pathophysiological mechanisms in COVID-19 patients with liver injury. We also discuss the development of chronic liver diseases during the progression of SARS-CoV-2 replication. Lastly, we explore management principles in COVID-19 patients with liver injury and liver transplantation.

The coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Hepatic involvement is common in SARS-CoV-2-infected individuals. It is currently accepted that the direct and indirect hepatic effects of SARS-CoV-2 infection play a significant role in COVID-19. In individuals with pre-existing infectious and non-infectious liver disease, who are at a remarkably higher risk of developing severe COVID-19 and death, this pathology is most medically relevant. This review emphasizes the current pathways regarded as contributing to the gastrointestinal and hepatic ailments linked to COVID-19-infected patients due to an imbalanced interaction among the liver, systemic inflammation, disrupted coagulation, and the lung.