The efficacy of targeted programmed cell death 1/programmed death ligand 1 (PD-1/PD-L1) monoclonal antibodies (mAbs) has been confirmed in many solid malignant tumors. The overexpression of PD-1/PD-L1 serves as a biomarker to predict prognosis and clinical progression. However, the role of PD-1 in patients with hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) remains indeterminate. Given that HBV is the most important cause for HCC, this study aimed to investigate the prognostic and clinicopathological value of PD-1 in HBV-HCC via a meta-analysis.

We searched PubMed, Embase, Scopus, the Cochrane Library, Web of Science and Google Scholar up to January 2021 for studies on the correlation between clinicopathology/prognosis and PD-1 in patients with HBV-HCC. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to investigate the prognostic significance of PD-1 expression. The odds ratios (ORs) and 95% CIs were determined to explore the association between PD-1 expression and clinicopathological features.

Our analysis included seven studies with 658 patients, which showed that high PD-1 expression was statistically correlated with poorer overall survival (HR=2.188, 95% CI: [1.262–3.115], p<0.001) and disease-free survival (HR=2.743, 95% CI: [1.980–3.506], p<0.001). PD-1 overexpression was correlated with multiple tumors (OR=2.268, 95% CI: [1.209–4.257], p=0.011), high level of alpha fetoprotein (AFP; OR=1.495, 95% CI: [1.005–2.223], p=0.047) and advanced Barcelona Clinic Liver Cancer (BCLC) stage (OR=3.738, 95% CI: [2.101–6.651], p<0.001).

Our meta-analysis revealed that the high level of PD-1 expression was associated with multiple tumors, high level of AFP and advanced BCLC stage. It significantly predicted a poor prognosis of HBV-HCC, which suggests that anti-PD-1 therapy for HBV-HCC patients is plausible.

The prognosis of hepatocellular carcinoma (HCC) is extremely poor; therefore, there is an urgent need for novel prognostic molecular biomarkers of HCC. The current investigation utilized circular (circ)RNA-associated competing endogenous (ce)RNAs analysis in order to identify significant prognostic biomarkers of HCC.

CircRNAs and mRNAs that were differentially expressed between normal and HCC tissues were identified. Their respective functions were predicted with Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. A nomogram was used for model verification.

A ceRNA network composed of differentially expressed circRNAs and mRNAs was constructed. Significant hub nodes in the ceRNA network were hsa_circ_0004662, hsa_circ_0005735, hsa_circ_0006990, hsa_circ_0018403 and hsa_circ_0100609. By using this information, a prognostic risk assessment tool was developed based on the expressions of seven genes (PLOD2, TARS, RNF19B, CCT2, RAN, C5orf30 and MCM10). Furthermore, multivariate Cox regression analysis revealed risk and T-stage parameters as independent prognostic factors. The nomograms that were constructed from risk and T-stage groups were used to further assess the prediction of HCC patient survival rates. The nomogram, which consisted of risk and T-stage scores assessment models, was found to be an independent factor for predicting prognosis of HCC.

Five circRNAs, including hsa_circ_0004662, hsa_circ_0005735, hsa_circ_0006990, hsa_circ_0018403 and hsa_circ_0100609, that may play key roles in the progression of HCC were identified. Seven gene signatures were identified, which were associated with the aforementioned circRNAs, including PLOD2, TARS, RNF19B, CCT2, RAN, C5orf30 and MCM10, all of which were significant genes involved in the pathophysiology of HCC. These genes may be used as a prognosticating tool in HCC patients.

Alzheimer’s disease (AD) is a neurodegenerative disorder with a complex pathology that is not completely understood. Over time, AD reduces one’s cortical and subcortical functioning. The incidence and prevalence of AD is projected to increase as the worldwide population continues to grow older. While advances in the field of neurology and medicine continue to improve, there are presently no novel therapeutic agents to prevent, halt, or cure patients suffering from AD. The utilization of biomarkers that aid the diagnostic algorithm, drug response monitoring and disease progression that add to further our understanding of the pathophysiology of neurodegenerative disease is vastly expanding. The significance of amyloid plaque deposition, tau pathology, and neurofibrillary tangle accumulation have been well-studied in the realm of neurodegenerative diseases for decades and are proposed biomarkers. However, it has been difficult to stratify physiological biomarkers of blood/plasma, cerebrospinal fluid, saliva/urine/hair/nail for diagnostic utility and overall understanding in the pathogenesis of neurodegeneration. We aim to review the most relevant, up-to-date biomarkers and their implications in AD.

It remains difficult to forecast the 180-day prognosis of patients with hepatitis B virus-acute-on-chronic liver failure (HBV-ACLF) using existing prognostic models. The present study aimed to derive novel-innovative models to enhance the predictive effectiveness of the 180-day mortality in HBV-ACLF.

The present cohort study examined 171 HBV-ACLF patients (non-survivors, n=62; survivors, n=109). The 27 retrospectively collected parameters included the basic demographic characteristics, clinical comorbidities, and laboratory values. Backward stepwise logistic regression (LR) and the classification and regression tree (CART) analysis were used to derive two predictive models. Meanwhile, a nomogram was created based on the LR analysis. The accuracy of the LR and CART model was detected through the area under the receiver operating characteristic curve (AUROC), compared with model of end-stage liver disease (MELD) scores.

Among 171 HBV-ACLF patients, the mean age was 45.17 years-old, and 11.7% of the patients were female. The LR model was constructed with six independent factors, which included age, total bilirubin, prothrombin activity, lymphocytes, monocytes and hepatic encephalopathy. The following seven variables were the prognostic factors for HBV-ACLF in the CART model: age, total bilirubin, prothrombin time, lymphocytes, neutrophils, monocytes, and blood urea nitrogen. The AUROC for the CART model (0.878) was similar to that for the LR model (0.878, p=0.898), and this exceeded that for the MELD scores (0.728, p<0.0001).

The LR and CART model are both superior to the MELD scores in predicting the 180-day mortality of patients with HBV-ACLF. Both the LR and CART model can be used as medical decision-making tools by clinicians.

Previous studies reported that serum resistin levels were remarkably changed in patients with nonalcoholic fatty liver disease (NAFLD) but the conclusions were inconsistent. The aim of this study was to investigate accurate serum resistin levels in adult patients with NAFLD.

A complete literature research was conducted in the PubMed, Embase, and Cochrane Library databases, and all the available studies up to 7 May 2020 were reviewed. The pooled standardized mean difference (SMD) values were calculated to investigate the serum resistin levels in patients with NAFLD and healthy controls.

A total of 28 studies were included to investigate the serum resistin levels in patients with NAFLD. Patients with NAFLD had higher serum resistin levels than controls (SMD=0.522, 95% confidence interval [CI]: 0.004–1.040, I2=95.9%). Patients with nonalcoholic steatohepatitis (NASH) had lower serum resistin levels than the healthy controls (SMD=−0.44, 95% CI: −0.83–0.55, I2=74.5%). In addition, no significant difference of serum resistin levels was observed between patients with NAFL and healthy controls (SMD=−0.34, 95% CI: −0.91–0.23, I2=79.6%) and between patients with NAFL and NASH (SMD=0.15, 95% CI: −0.06–0.36, I2=0.00%). Furthermore, subgroup and sensitivity analyses suggested that heterogeneity did not affect the results of meta-analysis.

This meta-analysis investigated the serum resistin levels in adult patients with NAFLD comprehensively. Patients with NAFLD had higher serum resistin levels and patients with NASH had lower serum resistin levels than healthy controls. Serum resistin could serve as a potential biomarker to predict the development risk of NAFLD.

The pathogenesis of liver fibrosis involves liver damage, inflammation, oxidative stress, and intestinal dysfunction. Indole-3-propionic acid (IPA) has been demonstrated to have antioxidant, anti-inflammatory and anticancer activities, and a role in maintaining gut homeostasis. The current study aimed to investigate the role of IPA in carbon tetrachloride (CCl4)-induced liver fibrosis and explore the underlying mechanisms.

The liver fibrosis model was established in male C57BL/6 mice by intraperitoneal injection of CCl4 twice weekly. IPA intervention was made orally (20 mg/kg daily). The degree of liver injury and fibrosis were assessed by serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and histopathology. Enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction (qPCR) were used to detect the inflammatory cytokines. The malondialdehyde (MDA), glutathione, glutathione peroxidase, superoxide dismutase, and catalase were determined via commercial kits. Hepatocyte apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. The expression of mRNA and protein was assayed by qPCR, Western blotting, or immunohistochemical staining.

After IPA treatment, the ALT and AST, apoptotic cells, and pro-inflammatory factor levels were enhanced significantly. Moreover, IPA intervention up-regulated the expression of collagen I, α-smooth muscle actin, tissue inhibitor of matrix metalloproteinase-1, matrix metalloproteinase-2, transforming growth factor-β1 (TGF-β1), Smad3, and phosphorylated-Smad2/3. Additionally, IPA intervention did not affect the MDA level. Attractively, the administration of IPA remodeled the gut flora structure.

IPA aggravated CCl4-induced liver damage and fibrosis by activating HSCs via the TGF-β1/Smads signaling pathway.

In the last decade, several second-line therapies followed by sorafenib in patients with advanced hepatocellular carcinoma (HCC) have been reported. But the outcomes were different from each other. This meta-analysis aimed to evaluate the efficacy and safety of the second-line therapies followed by sorafenib in patients with advanced HCC.

Embase (1974 to October 2019) and Ovid MEDLINE (1946 to October 2019) were searched for randomized clinical trials on second-line therapies followed by sorafenib in patients with advanced HCC. The quality of each study was assessed by the modified Jadad scale. Statistical analysis was carried out by RevMan5.3 software. Efficacy and safety were analyzed. Efficacy included overall survival (OS), disease control rate, time to progression, and progression-free survival.

Eight studies involving 3,173 patients were eligible. No difference in OS was found between the second-line treatment group and the control group (HR=0.87, 95% CI: 0.74–1.01, p=0.06). Disease control rate (relative risk (RR)=1.36, 95% CI: 1.16–1.60, p=0.0002), time to progression (HR=0.64, 95% CI: 0.51–0.81, p=0.0002) and progression-free survival (HR=0.60, 95% CI: 0.46–0.77, p<0.0001) were significantly improved by the second-line therapies. There was a slight difference in adverse events of any grade (RR=1.07, 95% CI: 1.00–1.14, p=0.03) between the two groups.

These second-line therapies followed by sorafenib may potentially improve the prognosis in patients with advanced HCC. Compared with other second-line therapies, regorafenib seemed to be more effective.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease in the world. The rising prevalence of nonalcoholic steatohepatitis (NASH) has led to a 170% increase in NASH cirrhosis as the listing indication for liver transplantation from 2004 to 2013. As of 2018, NASH has overtaken hepatitis C as an indication for liver transplantation in the USA. After liver transplantation, the allograft often develops recurrent NAFLD among patients with known NASH cirrhosis. In addition to recurrent disease, de novo NAFLD has been reported in patients with other indications for liver transplantation. In this review, we will discuss the risk factors associated with recurrent and de novo NAFLD, natural course of the disease, and management strategies after liver transplantation.

The ongoing coronavirus disease-2019 (COVID-19) pandemic has necessitated special considerations in the management of diseases. The way presence of pre-existing diseases or treatment for it predisposes to, alters course of, and changes the management of COVID-19, is of relevance and is being extensively studied. Autoimmune hepatitis (AIH) is unique in that it is an autoimmune disease mandating treatment with immunosuppressive drugs, as well as a liver disease with potential for varying degrees of underlying fibrosis. The use of immunosuppressive drugs could alter the risk of acquiring COVID-19, the clinical course and severity of COVID-19 and the degree of underlying liver fibrosis could alter the clinical outcomes of patients with COVID-19. In this review, we try to summarize key areas relevant in understanding and improving the clinical care of patients with AIH in the current pandemic. Special considerations required in the management of patients with AIH in COVID-19 hotspots have been outlined based on the current evidence.

The overall survival (OS) of hepatocellular carcinoma (HCC) remains dismal. Bioinformatic analysis of transcriptome data could identify patients with poor OS and may facilitate clinical decision. This study aimed to develop a prognostic gene model for HCC.

GSE14520 was retrieved as a training set to identify differential expressed genes (DEGs) between tumor and adjacent liver tissues in HCC patients with different OS. A DEG-based prognostic model was then constructed and the TCGA-LIHC and ICGC-LIRI datasets were used to validate the model. The area under the receiver operating characteristic curve (AUC) and hazard ratio (HR) of the model for OS were calculated. A model-based nomogram was established and verified.

In the training set, differential expression analysis identified 80 genes dysregulated in oxidation-reduction and metabolism regulation. After univariate Cox and LASSO regression, eight genes (LPCAT1, DHRS1, SORBS2, ALDH5A1, SULT1C2, SPP1, HEY1 and GOLM1) were selected to build the prognostic model. The AUC for 1-, 3- and 5-year OS were 0.779, 0.736, 0.754 in training set and 0.693, 0.689, 0.693 in the TCGA-LIHC validation set, respectively. The AUC for 1- and 3-year OS were 0.767 and 0.705 in the ICGC-LIRI validation set. Multivariate analysis confirmed the model was an independent prognostic factor (training set: HR=4.422, p<0.001; TCGA-LIHC validation set: HR=2.561, p<0.001; ICGC-LIRI validation set: HR=3.931, p<0.001). Furthermore, a nomogram combining the model and AJCC stage was established and validated, showing increased OS predictive efficacy compared with the prognostic model (p=0.035) or AJCC stage (p<0.001).

Our eight-gene prognostic model and the related nomogram represent as reliable prognostic tools for OS prediction in HCC patients.

Protein phosphatase 2A (PP2A) is associated with many cancers. This study aimed to clarify whether PPP2CA, which encodes the alpha isoform of the catalytic subunit of PP2A, plays a role in hepatocellular carcinoma (HCC) and to identify the potential underlying molecular pathways.

Based on bioinformatics, public databases and our in-house RNA-Seq database, we analyzed the clinical value and molecular mechanism of PPP2CA in HCC.

Data were analyzed from 2,545 patients with HCC and 1,993 controls without HCC indexed in The Cancer Genome Atlas database, the Gene Expression Omnibus database and our in-house RNA-Seq database. PPP2CA expression was significantly higher in HCC tissue than in non-cancerous tissues (standardized mean difference: 0.69, 95% confidence interval [CI]: 0.50–0.89). PPP2CA expression was able to differentiate HCC from non-HCC, with an area under the summary receiver operator characteristic curve of 0.79 (95% CI: 0.75–0.83). Immunohistochemistry of tissue sections confirmed that PPP2CA protein was up-regulated in HCC tissues. High PPP2CA expression in HCC patients was associated with shorter overall, progression-free and disease-free survival. Potential molecular pathways through which PPP2CA may be involved in HCC were determined using miRWalk 2.0 as well as analysis of Gene Ontology categories, Kyoto Encyclopedia of Genes and Genomes pathways, and protein-protein interaction networks.

PPP2CA is up-regulated in HCC and higher expression correlates with worse prognosis. PPP2CA shows potential as a diagnostic marker for HCC. Future studies should examine whether PPP2CA contributes to HCC through the candidate microRNAs, pathways and hub genes identified in this study.

The impact of coronavirus disease-2019 (COVID-19) on liver function remains to be fully elucidated. This study was designed to investigate such and determine the clinical significance in determining mortality risk.

A retrospective study was conducted in patients with COVID-19 from March 2020 to July 2020. Clinical details were retrieved from electronic medical records to obtain clinical characteristics, medical history, laboratory tests, therapeutic intervention, and outcome data.

A total of 184 patients with COVID-19 were included (median age: 45.5 years), comprised of 62.5% men. In total, 22 (12.0%) patients had severe infection and 162 (88.0%) had mild to moderate infection. Overall, 95 (51.6%) showed abnormal liver function test (LFT) and 17 (9.2%) showed normal LFT at admission. The median age, hospital stay, and LFT were significantly higher in severe vs. non-severe infection (p<0.001). Out of 12 deaths, the majority were due to severe infection (n=11). Deaths were also due to acute respiratory distress syndrome (n=5), cardiac reasons (n=3), and sepsis with multiorgan failure (n=3). The median age, hospital stay and number of intensive care unit admissions were higher in patients having abnormal LFT compared to normal LFT. Incidence of elevated aspartate aminotransferase (42.8% and 40.4%), alanine transaminase (43.7% and 41.6%), and hypoalbuminemia (71.4% and72.7%) at admission and discharge were more common in severe infection. The mean survival was significantly lower in severe infection compared to those with non-severe disease (17.2 vs. 52.3 days; p<0.001).

Incidence of abnormal liver function was higher in patients with severe COVID-19 and was associated with prolonged hospital stay; mortality was associated with severity of COVID-19. For ruling out the risk of liver injury, it is crucial to vigilantly monitor the liver function parameters in patients with COVID-19 admitted to hospital.

Biliary tract cancers (BTCs) comprise a group of heterogeneous poor prognosis cancers with increasing incidence recent years. The combination chemotherapy with cisplatin and gemcitabine is the first-line therapy for advanced BTC. There remains no accepted standard treatment in the second-line setting. Nowadays, more and more novel treatment strategies have entered development, with some encouraging results being seen. Here, we review the current treatment status and clinical characteristics of BTC, the role of immunotherapy in BTC as well as the design of clinical trials for oncology drugs for BTC which aim to focus on the future profiles of clinical care and resolution of BTC.

Hepatitis C virus (HCV) genotype (GT)3 infection is associated with a more rapid hepatic disease progression than the other genotypes. Hence, early HCV clearance slows down the disease progression and is important for improving prognosis in GT3-infected patients. Nevertheless, compared with other genotypes, GT3 is difficult-to-treat with direct-acting antivirals, especially in the presence of cirrhosis. Current guidelines recommend several regimens which have been proven to be effective in GT3-infected patients from the Western world (North America, Europe, and Oceania). In China, GT3 infection comprises 8.7–11.7% of the 10 million patients infected with HCV and has strikingly different characteristics from that in Western countries. Unlike the Western countries, where GT3a is the predominant subtype, GT3a and 3b each affect roughly half of Chinese GT3-infected patients, with 94–96% of the GT3b-infected patients carrying A30K+L31M double NS5A resistance-associated substitutions. Phase 3 clinical trials including GT3b-infected patients have suggested that GT3b infection is difficult to cure, making the regimen choice for GT3b-infected patients an urgent clinical gap to be filled. This review includes discussions on the epidemiology of HCV GT3 in China, recommendations from guidelines, and clinical data from both Western countries and China. The aim is to provide knowledge that will elucidate the challenges in treating Chinese GT3-infected patients and propose potential solutions and future research directions.

Renal transplant patients often require periodic imaging to evaluate the transplant vessel anastomosis for potential vascular complications. The use of non-contrast enhanced magnetic resonance angiography (NCE-MRA) techniques is encouraged in these patients because they are at increased risk of nephrogenic systemic fibrosis (NSF) due to their renal insufficiency. This study aimed to evaluate the performance of two NCE-MRA techniques (three-dimensional [3D] balanced steady-state free precession [bSSFP] with inversion recovery and quiescent-interval slice-selective [QISS]) for the evaluation of renal allograft vasculature in patients with clinical suspicion, or Doppler ultrasound, or both of arterial anastomotic stenosis.

A total of 43 patients were included in this retrospective study. Two radiologists independently scored the images from 3D bSSFP and QISS MRA sequences for image quality and confidence in anastomosis interpretation, and the degree of stenosis at the arterial anastomosis. Correlations with digital subtraction angiography (DSA) were carried out when available. In addition, inter-rater agreement was calculated.

In total, 43 patients underwent QISS and 3D bSSFP MRA. For QISS, all cases were adequate for evaluation. For 3D SSFP, 86% of cases were adequate for evaluation. There was a good-to-excellent inter-rater agreement for all scores and an excellent correlation between NCE-MRA and DSA results when available (12 patients).

QISS and 3D SSFP showed good inter-rater agreement for image quality and stenosis grade, with more cases being of adequate image quality that used QISS. Further study is required; however, NCE-MRA shows potential as a risk-free alternative to CTA and contrast-enhanced MRA (CE-MRA) for the evaluation of arterial anastomoses in renal transplant patients.

It is critical but challenging to predict the prognosis of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). This study systematically summarized and evaluated the quality and performance of available clinical prediction models (CPMs).

A keyword search of articles on HBV-ACLF CPMs published in PubMed from January 1995 to April 2020 was performed. Both the quality and performance of the CPMs were assessed.

Fifty-two CPMs were identified, of which 31 were HBV-ACLF specific. The modeling data were mostly derived from retrospective (83.87%) and single-center (96.77%) cohorts, with sample sizes ranging from 46 to 1,202. Three-month mortality was the most common endpoint. The Asian Pacific Association for the Study of the Liver consensus (51.92%) and Chinese Medical Association liver failure guidelines (40.38%) were commonly used for HBV-ACLF diagnosis. Serum bilirubin (67.74%), the international normalized ratio (54.84%), and hepatic encephalopathy (51.61%) were the most frequent variables used in models. Model discrimination was commonly evaluated (88.46%), but model calibration was seldom performed. The model for end-stage liver disease score was the most widely used (84.62%); however, varying performance was reported among the studies.

Substantial limitations lie in the quality of HBV-ACLF-specific CPMs. Disease severity of study populations may impact model performance. The clinical utility of CPMs in predicting short-term prognosis of HBV-ACLF remains to be undefined.

Intrahepatic cholangiocarcinoma (ICC) is a malignant tumor derived from intrahepatic bile duct epithelial cells. Accumulating studies report that microRNAs are widely involved in tumor migration and metastasis by regulation of target genes. miR-7-5p has been confirmed to inhibit tumor metastasis and to be related to prognosis for several malignant tumors. Our study investigated the underlying functions of miR-7-5p in ICC.

The expression of miR-7-5p in ICC tissues but also in ICC cell lines was analyzed by real-time PCR. By analyzing the relationship between the clinicopathological parameters of 60 ICC patients and the expression level of miR-7-5p, the effect of miR-7-5p on the prognosis was clarified. After transfected with miR-7-5p mimics or miR-7-5p inhibitor, cell counting kit-8 assay was applied to evaluate the cells proliferation, flow cytometry was applied to analyze the cells apoptosis, wound healing assay and transwell chamber assay were applied to analyze the cell invasion and migration. A luciferase reporter assay was identified the relationship of miR-7-5p and myeloid differentiation factor 88 (MyD88). Western blotting was used to analyze the proteins expression. And immunochemistry was performed to determine the expression of MYD88 in ICC tissues.

Our data showed the expression of miR-7-5p was down-regulated not only in ICC tissues but also in ICC cell lines compared with normal controls. Low expression of miR-7-5p was notably associated with poor prognosis in ICC patients. miR-7-5p negatively regulated cell proliferation, migration, invasion and apoptosis in ICC cells. We further verified that MyD88 was a novel target of miR-7-5p and was significantly overexpressed in ICC tissues. Overexpression of MyD88 counteracted the effects of miR-7-5p in ICC cells.

The present findings suggest that miR-7-5p plays a pivotal role in ICC invasion by regulating MyD88. Ampliative insight into the key factors of ICC invasion may result in the development of new treatment options for ICC.

Metabolic-associated fatty liver disease (MAFLD) is driven by high caloric intake and sedentary lifestyle. Migration towards high income countries may induce these driving factors; yet, the influence of such on the prevalence of MAFLD is clearly understudied. Here, we investigated the Fatty Liver Index (FLI), a proxy of steatosis in MAFLD, after migration of Ghanaian subjects.

Cross-sectional data of 5282 rural, urban and migrant participants from the Research on Obesity and Diabetes among African Migrants (also known as RODAM) study were analyzed with logistic regression for geographical differences in FLI and associations with type 2 diabetes mellitus (T2DM), waist-to-hip ratio, and 10-year predicted risk of atherosclerotic cardiovascular disease (ASCVD).

Both FLI and the proportion with an FLI indicative of MAFLD steatosis (FLI ≥60) were higher in migrants compared with non-migrants. Prevalence of elevated FLI (FLI ≥60) in non-migrant males was 4.2% compared to 28.9% in migrants. For females, a similar gradient was observed, from 13.6% to 36.6% respectively. Compared to rural residents, the odds for a FLI ≥60 were higher in migrants living in urban Europe (odds ratio [OR] 9.02, 95% confidence interval [CI]: 5.02–16.20 for men, and 4.00, 95% CI: 3.00–5.34 for women). Compared to controls, the ORs for FLI ≥60 were 2.43 (95% CI: 1.73–3.41) for male T2DM cases and 2.02 (95% CI: 1.52–2.69) for female T2DM cases. One-unit higher FLI was associated with an elevated (≥7.5%) 10-year ASCVD risk (OR: 1.051, 95% CI: 1.041–1.062 for men, and 1.020, 95% CI: 1.015–1.026 for women).

FLI as a proxy for MAFLD increased stepwise in Ghanaians from rural areas, through urban areas, to Europe. Our results clearly warrant awareness for MAFLD in migrant population as well as confirmation with imaging modalities.

Currently, insufficient clinical data are available to address whether low-level viremia (LLV) observed during antiviral treatment will adversely affect the clinical outcome or whether treatment strategies should be altered if LLV occurs. This study compared the clinical outcomes of patients with a maintained virological response (MVR) and patients who experienced LLV and their treatment strategies.

A retrospective cohort of 674 patients with chronic hepatitis B virus (HBV) infection who received antiviral treatment for more than 12 months was analyzed for the development of end-stage liver disease and treatment strategies during the follow-up period. End-stage liver disease included decompensated liver cirrhosis and hepatocellular carcinoma (HCC).

During a median 42-month follow-up, end-stage liver disease developed more frequently in patients who experienced LLV than in those who experienced MVR (7.73% and 15.85% vs. 0.77% and 5.52% at 5 and 10 years, respectively; p=0.000). The trend was consistent after propensity score matching. In the high-risk group of four HCC risk models, LLV patients had a higher risk of HCC development (p<0.05). By Cox proportional hazard model analysis, LLV was an independent risk factor for end-stage liver disease and HCC (hazard ratio [HR]=6.280, confidence interval [CI]=2.081–18.951, p=0.001; HR=5.108, CI=1.392–18.737, respectively; p=0.014). Patients achieved a lower rate of end-stage liver disease by adjusting treatment compared to continuing the original treatment once LLV occurred (p<0.05).

LLV is an independent risk factor for end-stage liver disease and HCC, and treatment adjustments can be considered.

Coronavirus disease 2019 (COVID-19) is a rapidly progressing pandemic causing death worldwide, particularly in individuals with comorbidities or in the elderly population. The increased pro-inflammatory cytokines in patients with severe COVID-19 can be considered macrophage activation syndrome or a cytokine storm. It has been reported that an autocrine loop of interleukin (IL) 1 beta (IL-1β) over-secretion leads to a cytokine storm of IL-6, IL-18, ferritin, interferon-gamma, etc. from macrophages. Several features of COVID-19, such as the cytokine profile including pro-inflammatory cytokine levels, subsets of immune cells, serological markers, and clinical symptoms resemble a cytokine storm commonly triggered by viral infections. Although the pathophysiology and management of severe COVID-19 remains uncertain, the use of an easily obtained autologous anti-inflammatory cocktail, termed autologous conditioned serum (ACS), can be hypothesized. ACS consists of a variety of anti-inflammatory cytokines, including mainly IL-1 receptor antagonist (IL-1Ra; as much as 140-fold greater than plasma), and several growth factors. Post-mortem findings of COVID-19 patients reveal that the main pathological events are localized to the alveoli. Therefore, administering ACS via the same pathway as the viral trigger may have a positive impact on treatment. ACS should be discussed for the management of COVID-19 to target and lessen the overactive immune response while still allowing time for the host immune system to clear the virus. To balance the cytokine storm, it could be suggested to administer ACS by the same pathway as the viral trigger, using a nebulizer to directly reach the most intensely affected location: the alveoli.