Hepatitis Monthly
Volume:22 Issue: 1, Dec 2022

High-risk behaviors in people with severe mental illnesses, such drug injection by shared equipment and unprotected sex, expose them to the risk of blood-borne infections such as hepatitis B virus (HBV) and hepatitis C virus (HCV) infections.

This study aimed to determine the prevalence of HBV and HCV serum markers in people with severe mental illnesses in Tehran, Iran.

In this cross-sectional study, people with mental illnesses, such as schizophrenia, bipolar disorder, and depression, were studied. The participants were recruited using a non-random convenience sampling method from Roozbeh and Razi hospitals in Tehran between December 2019 and March 2020. Blood samples were evaluated for HCV-Ab, HBs Ag, HBs Ab, and HBc Ab using an enzyme immunoassay technique.

A total of 257 participants were recruited for this study; their mean age was 35.77 years, and 70.0% of whom were male. Bipolar disorder (40.5%) and schizophrenia (35.8%) were the most frequent severe mental disorders in the participants. The prevalence of HBV and HCV seromarkers was as follows: HBs Ag: 0.3% (95% CI: 0.0 - 2.0%), HBc Ab: 7.3% (95% CI: 4.6 - 11.3%), HBs Ab: 18.7% (95% CI: 14.1 - 24.0%), and HCV Ab: 3.1% (95% CI: 1.3 - 6.9%). In logistic regression analysis, tattooing (OR = 4.94, 95% CI: 1.73 - 14.13) and age (OR= 1.06, 95% CI: 1.01 - 1.11) were associated with HBV infection (HBc Ab positivity), and only tattooing (OR= 6.33, 95% CI: 1.19 - 33.80) was significantly associated with exposure to HCV.

The results of this study showed that the prevalence of HBsAg positivity in people with severe mental illness was not higher than that in the general population of Iran; however, HCV Ab positivity was more prevalent in people with severe mental illness than in the general population of Iran. Preventive, diagnostic, and therapeutic interventions for HCV infection are needed in this population in Iran.

Past research has found that fibroblast growth factor 19 (FGF19) is associated with several hepatic disorders, such as alcoholic liver disease and primary biliary cirrhosis. However, there is currently a lack of relevant studies on the relationship between FGF19 and hepatitis B virus (HBV)-related liver disease.

This study aimed to assess the role of serum FGF19 as a new biomarker for HBV-related liver disease and provide scientific data to show the clinical value of this biomarker.

A retrospective study included 37 patients with chronic hepatitis B (CHB), 33 patients with HBV-related cirrhosis (HBV-cirrhosis), and 32 patients with HBV-related hepatocellular carcinoma (HBV-HCC). Furthermore, 33 normal people were randomly selected as healthy controls. The serum levels of FGF19 were measured by ELISA.

Serum FGF19 levels were increased sequentially in the CHB group, HBV-cirrhosis group, and HBV-HCC group. Furthermore, serum FGF19 levels positively correlated with alpha-fetoprotein, prothrombin time, international normalized ratio, total bilirubin, direct bilirubin, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl-transferase, alkaline phosphatase, total bile acid, serum markers for liver fibrosis, ascites, cirrhosis, Child-Pugh classification and model for end-stage liver disease sodium (MELD-Na) score, while negatively correlated with platelet count, prothrombin activity, and albumin. The diagnostic threshold of serum FGF19 for HBV-related HCC was 165.32 pg/mL, with a sensitivity of 81.25% and specificity of 58.57%.

Serum FGF19 levels are positively associated with cholestasis, hepatocyte damage, and liver fibrosis but negatively correlated with liver synthetic function and liver functional reserve in HBV-related liver disease. Diverse changes in serum FGF19 may be used as a predictive marker for the progression of HBV-related liver disease. In addition, serum FGF19 has a potential role in monitoring carcinogenesis in patients with HBV-related liver disease.

Cytokines play an important role in tumor progression, but studies have shown mixed results regarding the role of cytokines in predicting the early response to transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC).

This study aimed to explore the correlation between plasma levels of cytokines and early tumor response in HCC patients undergoing TACE.

Thirty HCC patients enrolled in this study from the department of liver disease of a general hospital from June 2020 to January 2021. Plasma samples were sampled at baseline and 7 days after TACE for cytokine detection by cytometric bead array (CBA). At 4 - 6 weeks after TACE, the objective response of HCC patients was confirmed according to response evaluation criteria in solid tumors (RECIST). Potential factors such as various cytokines and some clinical parameters were analyzed by univariate and multivariate analysis. The predictive effects of different factors in HCC patients undergoing TACE were analyzed by the receiver operating characteristic (ROC) curve.

Plasma levels of post-TACE interleukin-10 (IL-10) were statistically significantly higher than baseline IL-10 levels. The level of plasma IL-10 after TACE was an independent risk factor for early tumor response. The patients with low plasma IL-10 levels after TACE had a favorable prognosis. Receiver operating characteristic curve analysis showed that post-TACE IL-10 had a high predictive value (area under the curve = 0.769, 95% confidence interval (CI): 0.598 - 0.939). A high level of plasma IL-10 after TACE was correlated with alpha-fetoprotein (AFP) level (P = 0.037) and post-TACE alanine aminotransferase (ALT) (r = 0.368, P = 0.045). Post-TACE plasma IL-10 did not correlate with age or tumor metastasis.

Our findings demonstrated that post-intervention plasma IL-10 levels could predict short-term outcomes independently after TACE. These findings were helpful in identifying the patients who might benefit from TACE.

Context:

 When nucleos(t)ide analogues (NAs) were applied clinically to manage chronic hepatitis B virus infection, the prognosis of chronic hepatitis B (CHB) patients greatly improved. However, certain CHB patients with normal alanine aminotransferase (ALT) levels were not used to be considered as the population with the need for antiviral treatment.

This systematic review and meta-analysis collected and analyzed data from clinical trials to assess and compare the efficacy of antiviral treatment among patients with elevated and normal ALT levels.

A systematic search was performed to gather studies published from 1990.01 to 2022.08 in PubMed and Web of Science databases. The quality of the literature was assessed, and 16 studies were included for further analysis. Basic information on included studies and study populations was collected. A meta-analysis was carried out to evaluate three major outcomes of viral response, hepatitis B envelope antigen (HBeAg) loss, and HBeAg seroconversion after NAs treatment based on data extracted from these studies. Odds ratios (ORs) with 95% confidence intervals (CIs) for all outcomes were calculated using fixed-effects models.

In the 16 relevant studies, 5,345 patients met the inclusion criteria, including 3,687 patients receiving NAs treatment. All patients were grouped into one with elevated ALT and another with normal ALT based on whether their pretreatment ALT levels > 1*upper limit of normal (ULN). For patients receiving lamivudine, the viral response showed no significant difference between the groups with elevated and normal ALT levels (pooled log OR: 0.51 [-0.23 - 1.26], P = 0.79); the pooled log OR for HBeAg loss was 1.19 (0.63 - 1.76, P = 0.03) and pooled log OR for HBeAg seroconversion was 2.19 (0.91 - 3.47, P = 0.40). For patients receiving first-line therapy with tenofovir disoproxil fumarate (TDF) and entecavir (ETV), the viral response showed no significant difference between the two groups: Pooled log OR (0.38 [-0.22 - 0.97], P = 0.10). The pooled log OR for HBeAg loss and HBeAg seroconversion was (-0.07 [-0.81 - 0.67], P = 0.68) and (0.40 [-0.84 - 1.63], P = 0.88), respectively.

The efficacies of first-line therapy with TDF and ETV treatments were similar in groups with elevated and normal ALT levels for the outcomes of viral response and HBeAg loss. These findings may support further treatment of CHB patients with normal ALT levels.

Early diagnosis of hepatic lesions can result in more successful treatment.

The present study aimed to diagnose hepatic space-occupying lesions by sonography in Guilan Cohort Center participants.

In this cross-sectional prospective epidemiological research studies of Iranian adults (PERSIAN) Guilan cohort study (Sowme'eh Sara, Guilan, Iran) conducted in 2014 - 2017, the sample included 960 individuals of both genders, aged 35 - 60 years. A radiologist examined all individuals with sonography to determine hepatic space-occupying lesions. Demographical and clinical characteristics were recorded via a questionnaire. Data analysis was performed using SPSS software (version 16).

Only 2.3% of the patients were diagnosed with hepatic lesions such as hemangioma, hepatic cysts, and other lesions with frequencies of 1.1%, 0.8%, and 0.4%, respectively. Also, there was a significant relationship between gender and the presence of hepatic lesions (P < 0.05). The frequencies of hepatic lesions were 1.7% and 3.6% in men and women and 1.6%, 2.5%, and 4.4% in the age groups of 35 - 45, 45 - 55, and over 55 years, respectively.

Hemangioma was the most common hepatic lesion diagnosed in ultrasonography examinations. Moreover, the only factor influencing the frequency of hepatic lesions was gender, which was found twice more in women than in men.

Metabolic-associated fatty liver disease (MAFLD) is a common cause of liver-related mortality and morbidity worldwide. However, there is a paucity of literature on the relationship between cardiovascular disease (CVD) risk factors and quality of life (QoL) in patients with MAFLD.

This study aimed to examine the association between QoL and CVD risk factors in an Iranian MAFLD population.

This study was conducted on MAFLD patients, referred to the gastroenterology clinic of a general hospital from September 2017 until September 2018. The QoL and Framingham Risk Score (FRS) were determined using the WHOQOL-BREF questionnaire and an online web calculator, respectively. A hierarchical multiple linear regression model was developed to evaluate the association between QoL and FRS after adjusting for the sociodemographic characteristics.

This study was performed on 200 participants. All domains of QoL were associated with older age, hypertension, smoking, diabetes mellitus, higher systolic blood pressure, and lower high-density lipoprotein levels in the univariate regression analysis (P < 0.05 for all). Meanwhile, FRS was adversely correlated with the total QoL score (correlation coefficient: -0.49; 95% CI: -0.61, -0.35; P < 0.001). After adjusting for the sociodemographic variables, the results of the hierarchical multiple linear regression model showed that age, smoking, diabetes mellitus, hypertension, and FRS were correlated with the overall QoL score (P < 0.05 for all). Hypertension was the main predictor of the total QoL score (B = -5.51, 95% CI: -7.18, -3.68; P < 0.05). A higher FRS was inversely associated with the physical domain of QoL (B = -0.05, 95% CI: -0.09, -0.01; P < 0.05), the environment domain of QoL (B = -0.04, 95% CI: -0.09, -0.01; P < 0.05), and the total score of QoL (B = -0.04, 95% CI: -0.08, -0.02; P < 0.05).

According to the results of this study, a higher risk of developing CVD may reduce QoL in patients with MAFLD. Hypertension, diabetes mellitus, and smoking were the key predictive determinants of QoL in this population. Further studies are suggested to determine if modification of the mentioned risk factors can improve QoL in MAFLD patients.

 Hepatocellular carcinoma (HCC) is a prevalent and life-threatening tumor with high morbidity and mortality. Proper prediction and prognosis are incredibly stressed to diagnose HCC and increase patient survival.

 This research aims to evaluate gene expression levels of pre-differentiated transcripts for those suffering from chronic hepatitis B (CHB) and HCC.

 To examine the previously analyzed peripheral blood mononuclear cells (PBMCs) transcriptomic array data, we selected seven differentially expressed genes (DEGs) in normal versus CHB and CHB versus HCC (CD44, SP3, USP8, E2F2, UFM1, IFN regulative factor binding protein 2 (IRF2BP2), and T-cell intracellular antigen 1 (TIA1)). The study included individuals with treatment-naïve CHB (n = 30) and primary HCC (n = 25) and healthy controls (n = 15). Subsequently, the expression of genes was assayed using qRT-PCR. A phylogenetic evaluation was performed using direct sequencing of HBsAg.

 In HCC patients, 60% (n = 15) were HBeAg-positive. HBeAg was negative in all CHB patients, but all were anti-HBe-positive. The hepatitis B virus (HBV) load of HCC patients was more than that of CHB subjects. All patients were of the Iranian race and HBV D genotype. The expression of five transcriptional markers (CD44, SP3, USP8, E2F2, and UFM1) was higher in HCC patients than in CHB and healthy subjects, which was similar to the initial microarray data analysis.

 Transcriptional signatures may be related to the pathogenesis of HCC and used as diagnostic biological markers for the initial monitoring and prediction of HCC.

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, and different hepatitis viruses might affect the prognosis of patients with HCC.

This study aimed to reveal the differences in the postoperative prognosis of patients with hepatitis B virus-related HCC (HBV-HCC), hepatitis C virus-related HCC (HCV-HCC), and non-HBV non-HCV hepatocellular carcinoma (NBNC-HCC).

The databases PubMed, Embase, Cochrane, Web of Science, and Scopus were searched for articles published until April 2022. Stata software version 12 and Review Manager version 5.4 were used to conduct the meta-analysis, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was adopted in this study.

In the present study, 26 papers on a total of 20381 participants who met the inclusion criteria were analyzed. The 5-year overall survival in the HBV-HCC and HCV-HCC groups was lower than in the NBNC-HCC group (HBV-HCC vs. NBNC-HCC, P = 0.005; HCV-HCC vs. NBNC-HCC, P = 0.001). Patients with HBV-HCC and HCV-HCC had worse 5-year recurrence-free survival than patients with NBNC-HCC (HBV-HCC vs. NBNC-HCC, P = 0; HCV-HCC vs. NBNC-HCC, P = 0). In addition, the 5-year recurrence-free rate in the HCV-HCC group was lower than in the HBV-HCC group (P = 0). The observed association between serum alpha-fetoprotein levels and the postoperative prognosis was inconsistent in different subgroups.

Patients with NBNC-HCC had a significantly better postoperative prognosis than those with virus-related HCC. The alpha-fetoprotein levels significantly correlated with the postoperative prognosis of patients with HCC.

SLC10A1 codes for the sodium taurocholate cotransporting polypeptide (NTCP). The SLC10A1S267F mutation is associated with loss of function of bile acid (BA) uptake and defined as a new type of hypercholanemia. This kind of hypercholanemia is characterized by high levels of serum BA. However, limited studies have been conducted on this topic.

This study aimed to describe the biochemical and bioinformatic characterization of patients with an SLC10A1S267F mutation, as well as to dissect pathogenesis in hypercholanemia.

In this study, a total of 12 individuals (including 5 homozygous, 3 heterozygous, and 4 wild-type individuals) were recruited. Whole-genome sequencing (WGS) and Sanger sequencing were used to confirm the genotype. Tests of liver function, renal function, and serum lipid level, in addition to routine blood tests, were performed to evaluate the clinical consequences of patients with an SLC10A1S267F mutation. The ClinVar website and protein prediction tools were used to analyze other cholesterol and BAs related gene mutations in SLC10A1S267F patients, as well as to evaluate their possible effects on serum BA levels of patients.

All SLC10A1S267F homozygous patients displayed high levels of BAs. Liver and renal functions were generally normal. According to previous reports, homozygous patients are prone to vitamin D deficiency and deviated blood lipids. However, all homozygous individuals had normal levels of blood lipids, thyroid hormones, and vitamin D (25(OH)D). Moreover, except for the SLC10A1S267F mutation, according to the WGS results, multiple gene mutations were found in 5 homozygous and might affect the level of BAs, but the SLC10A1S267F mutation still is the most important reason resulting in a high level of BAs.

This study provided a more detailed description of the SLC10A1S267F mutation-induced hypercholanemia, delivering a new idea that there might be some mutations in SLC10A1S267F homozygotes, probably influencing BA metabolism.

Acute liver failure (ALF) is caused by massive hepatocyte death and accompanied by severe coagulation disorder and encephalopathy. It often leads to multiple organ failure and subsequently death. However, the association between ALF and other organ failure remains unclear.

Here, we evaluated patients with acute liver injury (ALI) and elevated pancreatic enzymes to demonstrate the association between ALI and pancreatic disorder.

We conducted a single-center retrospective study to analyze patients with ALI. Between 2012 and 2017, 163 patients with ALI were treated in our hospital. We stratified patients based on whether serum amylase and lipase were elevated above 1.5 times the upper limit of normal. We compared the baseline characteristics, severity, prognosis, and serum cytokine levels between the two groups.

Of the 163 patients, 75 (54.0%) presented elevated pancreatic enzymes above 1.5 times the upper limit of normal. Computed tomography imaging findings associated with pancreatitis were observed in 29 patients (17.8%). The elevation of pancreatic enzymes was associated with ALI severity. High level of serum tumor necrosis factor-alpha (TNF-α) was associated with the elevation of pancreatic enzymes (elevation group Vs. no elevation group: 134.0 ± 177.2 pg/mL Vs. 89.4 ± 159.8 pg/mL).

The elevation of pancreatic enzymes was often accompanied by ALI and associated with ALI severity. TNF-α signaling was involved in the elevation of pancreatic enzymes. It is possible that the pancreatic disorder reflected ALI severity, consequently correlated with mortality, and did not directly aggravate ALI pathogenesis. These findings provide novel insights into the pathogenesis of ALF.

The epidemiology of Hepatitis B (HBV) and C (HCV) remains poorly documented in Malaysia. Available statistics are based on data from mostly small studies in special populations.

In this study, we provide estimates of the proportion of people who are positive for HBs Antigen (HBsAg) and anti-HCV antibody (Ab) among participants in a community screening campaign.

A total of 10,914 subjects participated in the hepatitis screening campaign organized by Hepatitis Free Pahang in 2018 and 2019. A low-cost point-of-care test, which has previously been validated, was used to screen for HBsAg and anti-HCV Ab. All screened positive subjects were recalled to undergo confirmatory serologic tests (enzyme-linked immunosorbent assay) and nucleic acid tests (Real-time Polymerase Chain Reaction.

We estimated that 1.17% of adults aged 20 or older who participated in the screening campaign were positive for HBsAg+, and only 0.71 percent were positive for anti-HCV Ab+. Young adults below 30 years of age had a very low proportion of HBsAg+ (0.09%). Women had a lower proportion of HBsAg+ and HCV- Ab+, Chinese had the highest proportion of HBsAg+, while Malay had the highest proportion of anti-HCV Ab+.

Among adult participants of screening in Malaysia, chronic HBV is still common, especially among older and Chinese people. Adults with positive anti-HCV Abs are much less common.

Gabapentin, originally an antiepileptic agent, was found to have anti-cancer activity on multiple cancer cells. However, its effects on hepatocellular carcinoma (HCC) and associated molecular mechanisms are unclear.

In this study, we investigated the anti-cancer effects of gabapentin against HCC cells in vitro and in vivo.

Human HCC cells were inoculated with various levels of gabapentin for 24 and 48 h. We utilized the MTT assay to detect the proliferation of HCC cells after gabapentin treatment. The effect of gabapentin on the migration of HCC cells was detected by transwell migration assay. We established a model of subcutaneously transplanted HCC in nude mice and observed the impact of gabapentin on HCC cell tumorigenicity in vivo. The changes in RNA expression in gabapentin-treated HCC cells were evaluated by RNA sequencing analysis, and the results were analyzed and further validated by qRT-PCR.

Gabapentin significantly inhibited the proliferation of a variety of human HCC cells in a time- and dose-dependent approach. After treatment with 10 mM gabapentin for 12 h, the transendothelial migration of HCC cells via membrane remarkably reduced. Three weeks after the hypodermic transplanting of HCC in nude mice with Huh7 cell line, the gabapentin-treated group had a dramatic decrease in mean tumor volume and weight relative to the controls. Relative to the normal Huh7 cell line, the results of RNA sequencing of Huh7 cells treated with gabapentin for 24 h showed the differential enrichment of genes involved in "energy metabolism", "cancers", "signal transduction", and "folding, sorting, and degradation". The genes CDH11 and ARHGAP15 related to cell migration were further verified by qRT-PCR.

Our results suggested that gabapentin has an inhibitory effect on the growth, migration, and tumor formation of hepatoma cells, and the mechanism of gabapentin’s inhibition on HCC cells may be related to some signaling pathways, which will lay a foundation for the future studies on branched-chain aminotransferase 1 (BCAT1) as a target for HCC treatment.

Although various studies have assessed the correlation between gamma-glutamyl transferase (GGT) and cardiometabolic risk factors in obesity, no research has differentiated among metabolically-healthy obese (MHO) and metabolically unhealthy obese (MUHO), metabolically-healthy lean (MHL), and metabolically-unhealthy lean (MUHL).

Accordingly, this study evaluated the correlation between GGT and cardiometabolic phenotypes among healthcare workers.

In this study, there were anthropometric measurements as well as the measurements of fasting blood sugar (FBS), GGT, cholesterol, triglyceride (TG), high lipoprotein density (HDL), and blood pressure in 1458 healthcare workers enrolled in the Azar Cohort Study. Metabolic syndrome (MetS) was defined according to the National Cholesterol Education Program Adult Treatment Panel III (ATP III). Accordingly, the participants were divided into four cardiometabolic phenotypes.

In this cross-sectional study, there was a significant difference in the prevalence of cardiometabolic phenotypes regarding the GGT tertiles (P ≤ 0.001). The highest prevalence of MHO was observed in the third GGT tertile. The mean waist circumference, TG, FBS, HDL, and systolic and diastolic blood pressure levels increased in the MHO, MUHO, and MHL groups in a dose dependent manner with an increase in the GGT tertiles (P < 0.05). In comparing the highest and lowest GGT tertile, the risk of MHO and MUHO increased by 2.84 (95%CI 2.01 - 4.01) and 9.12 (95%CI 5.54 - 15), respectively. However, the correlation between the GGT tertile and MUHL did not reveal a similar trend. The ROC curve shows the cutoff value of 18.5 U/L for GGT, which allowed us to distinguish between the MUHO and MHO individuals.

The findings revealed that GGT can indicate the risk of MetS as such, it can be used to detect at-risk MHO individuals and administer proper interventions.

 This study aimed to explore the correlations of programmed death-1 (PD-1) and CC chemokine ligand 20 (CCL20) with Treg/T helper 17 (Th17) balance in patients with HBV-ACLF.

 In this cross-sectional study, 50 patients with HBV-ACLF and 50 cases with chronic hepatitis B (CHB) diagnosed from February 2021 to February 2022 were selected, and another 50 healthy volunteers who received physical examinations in the same period were selected as a control group. The expression levels of PD-1, CCL20, and Treg/Th17 cytokines were detected by Western blotting, immunoturbidimetry, and enzyme-linked immunosorbent assay (ELISA), respectively. The correlations of PD-1 and CCL20 with Treg/Th17 cytokines were explored by Pearson analysis. The predictive values of PD-1, CCL20, and Treg/Th17 cytokines for the prognosis of HBV-ACLF patients were analyzed.

 The expression levels of PD-1 and CCL20 were higher in the HBV-ACLF group than in the CHB and control groups (P < 0.05). Severe HBV-ACLF patients had higher levels of PD-1 and CCL20 compared with mild and moderate HBV-ACLF patients (P < 0.05). Hepatitis B virus-related acute-on-chronic liver failure patients with poor prognosis had higher levels of PD-1 and CCL20 than those with good prognosis (P < 0.05). The levels of transforming growth factor β (TGF-β), interleukin 10 (IL-10), IL-23, and tumor necrosis factor α (TNF-α) were higher in the HBV-ACLF group than in the CHB and control groups (P < 0.05). The levels of PD-1 and CCL20 in the HBV-ACLF group were positively correlated with those of Treg/Th17 cytokines (TGF-β, IL-10, IL-23, and TNF-α; P < 0.05). The combined detection of PD-1, CCL20, and Treg/Th17 cytokines had higher sensitivity and lower specificity than single detection in predicting the prognosis of HBV-ACLF patients (P < 0.05).

 The expression levels of PD-1 and CCL20 are higher in HBV-ACLF patients, being correlated with Treg/Th17 balance. The combined detection of PD-1, CCL20, and Treg/Th17 cytokines has a higher value for predicting the prognosis of HBV-ACLF patients.

Mesenchymal stem cells (MSCs) are the most promising tools for cell treatment and human tissue regeneration, e.g., in liver fibrosis. Mesenchymal stem cells repair tissue damage through paracrine mediators such as exosomes. Types and concentrations of inflammatory mediators, including transforming growth factor-beta (TGFβ1), in MSCs microenvironment can affect MSCs’ function and therapeutic potency.

This experimental study aimed to explore the effects of Wharton jelly MSCs (WJ-MSCs) exosomes on fibrotic gene expression and Smad2/3 phosphorylation (phospho-Smad2/3 (p-Smad2/3)). Moreover, we further investigated whether WJ-MSCs pretreatment with different concentrations of TGFβ1 changes the anti-fibrotic properties of their exosomes.

After isolation from the umbilical cord, WJ-MSCs were characterized by observing differentiation and measuring surface biomarkers using flowcytometry. The WJ-MSC-derived exosomes were extracted and identified using transmission electron microscopy (TEM), dynamic light scattering (DLS), and western blotting. Real-time PCR and western blot for extracellular matrix (ECM) and p-Smad2/3 expression detection were used to investigate the effect of exosomes from untreated and TGFβ1-pretreated WJ-MSCs on activated hepatic stellate cells (HSCs).

Phospho-Smad2/3, α-smooth muscle actin (α-SMA), and collagen1α1 levels were enhanced following treatment with TGFβ1, whereas E-cadherin was decreased. However, the outcomes were reversed after treatment with WJ-MSC-derived exosomes. Exosomes from TGFβ1-pretreated WJ-MSCs induced a significant decrease in p-Smad2/3 levels in activated HSCs, accompanied by the upregulation of E-cadherin gene expression and downregulation of α-SMA and collagen1α1 when compared to untreated WJ-MSC-derived exosomes. The p-Smad2/3 proteins were significantly decreased (fold change: 0.23, P-value < 0.0001) after exposure to low-dose TGFβ1-pretreated WJ-MSC-derived exosomes (0.1 ng/mL), showing the best effect on activated HSCs.

Exosomes derived from untreated WJ-MSCs could regress TGFβ-Smad2/3 signaling and the expression of fibrotic markers in activated LX-2 cells. However, these effects were significantly profound with applying exosomes derived from 0.1 ng/mL TGFβ-pretreated WJ-MSCs. We also observed the dose-response effects of TGFβ on WJ-MSCs-derived exosomes. Therefore, exosomes derived from TGFβ-pretreated WJ-MSCs may be critical in improving fibrosis and benefit liver fibrosis patients.

 Chronic hepatitis B (CHB) patients who are under the treatment of antiviral agents should be monitored in routine control visits. However, during the COVID-19 pandemic, the visits were interrupted.

 This study aimed to investigate whether these patients were affected regarding clinical, laboratory, and treatment outcomes.

 This prospective study consisted of CHB patients aged > 18 who were applied to 3 tertiary centers between 14 February and 30 March 2022. The patients were selected from the ones who regularly applied to outpatient clinics and under the treatment of antiviral agents before the pandemic. The demographic and laboratory values, including serologic, biochemistry, and molecular results, were compared between the 2 groups who came and did not come to control visits.

 A total number of 220 patients were included. More than half (n = 142, 64.5%) were female. The median age was 44 years (19 - 73). A hundred and forty-two (64.5%) patients did not come to control visits during the pandemic. The most common reason was anxiety about COVID-19. The tenofovir treatment was replaced with entecavir (ETV) due to osteopenia and with alafenamide due to osteopenia and/or renal failure. The previous agents were re-started in 27 (79.5%) patients who discontinued the treatment.

 The COVID-19 pandemic negatively impacted the follow-up of CHB patients. In this regard, 15.5% of patients stopped their treatments. The patients who stopped their follow-ups and continued tenofovir disoproxil fumarate (TDF) had proteinuria and decreases in bone mineral density (BMD) and estimated glomerular filtration rate (eGFR) levels.

Chronic hepatitis C virus (HCV) infection affects 58 million people globally. The frequency of HCV infection in the general Iranian population is less than 0.5%; however, a concentrated epidemic was reported among people who use drugs, particularly those with a history of drug injection.

This cross-sectional study was performed to assess the prevalence of HCV infection among high-risk groups outside of prison in northeastern Iran.

A total of 962 participants in Razavi Khorasan province were enrolled from 2018 to 2022. They included drug users referred to drug treatment and harm reduction centers and individuals with a history of crimes such as drug use or imprisonment who worked in a private industrial unit. Serum anti-HCV antibodies were assessed using a rapid or ELISA kit, and seroreactive samples were confirmed by single-step reverse transcriptase or qualitative real-time polymerase chain reactions. A P-value < 0.05 was considered statistically significant.

The mean age of 707 males and 255 females was 39.8 ± 10.2 years. Anti-HCV antibodies were detected from 129 samples (13.41%), of which 107 were available for polymerase chain reaction testing. HCV RNA was detected in 88 cases (75.2%); the total viremia rate was calculated as 9.26% (88/950). Logistic regression analysis revealed that HCV infection among drug users was significantly associated with older age (P = 0.002), being single (P = 0.009), and history of drug injection (P < 0.001) or incarceration (P = 0.04).

The findings showed a considerably high prevalence of HCV infection among people who use drugs in northeastern Iran. To achieve the global goal of viral hepatitis elimination by 2030, we strongly recommend stricter screening and treatment of this infection among such hard-to-access populations in Iran.

 Immunoassayis still used to detect hepatitisCvirus (HCV) antibodies in donated blood inmanydeveloping countries. However, an immunoblotting confirmation test is needed to confirm positive results. Objectives: We compared the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of nucleic acid testing and HCV core antigen (HCVcAg) detection in the serum samples of blood donors with HCV antibodies to determine active infection.

Overall, 90serumsamplesfrom blood donors referred to Fars province, Iran, Blood Transfusion Center duringMarch2017- March 2019 and initially tested for HCV antibodies were included in the study. Enzyme immunoassays were used to detect the HCV antigen and anti-HCV antibody. A commercial reverse transcription-polymerase chain reaction (RT-PCR) kit was used to quantify HCV RNA. The HCV genotypes were also determined by DNA sequencing. In order to compare the HCVcAg detection method with the RT-qPCR reference method, sensitivity, specificity, performance, PPV, and NPV were calculated.

Out of 90 serum samples, 73 were positive for anti-HCV antibody, and 17 sera were negative. The HCVRNA was detected in 60 (82%) of anti-HCV antibody-positive samples, whereas the HCVcAg test detected HCV antigen in 54 (74%) of the samples, indicating a significant correlation between the two assays (r = 0.86). The overall sensitivity and specificity for HCVcAg detection method were 93.85% [95% confidence interval (CI): 84.99 - 98.3%] and 100% (95% CI: 94.64 - 100%), respectively. Based on the statistical analysis, the accuracy of the antigen detection test was 94.83% (95% CI: 87.26 - 98.58%). Moreover, the agreement between HCV RNA detection using RT-qPCR and HCVcAg detection was 97.78% (kappa value: 0.94).

The sensitivity and specificity of HCVcAg detection in blood donors were ideal compared to the RT-qPCR reference method. However, the method should be tested on more HCV antibody-positive and -negative samples. Furthermore, our study revealed a significant association between the number of RT-qPCR-positive cases and the cases diagnosed by the HCVcAg detection method for screening and detecting active HCV infection in blood donors.

Nonalcoholic fatty liver disease (NAFLD) is the most common type of chronic liver disease worldwide. Left untreated, it can be a risk factor for developing cirrhosis or hepatocellular carcinoma (HCC). Although experts have made many efforts to find the underlying mechanisms of NAFLD, they remain a mystery.

This study aimed to distinguish common gene signatures and pathways in the human liver during NAFLD progression through systems biology.

In this study, the researchers selected three microarray datasets, GSE48452, GSE63067, and GSE89632, from the NCBI GEO database to explore differentially expressed genes (DEGs) among healthy controls, simple steatosis, and nonalcoholic steatohepatitis (NASH) patients. Furthermore, protein-protein interaction (PPI) networks and pathway enrichment analyses were used to detect common genes and biological pathways in different stages of NAFLD.

The current study included 45 healthy participants, 36 simple steatosis patients, and 46 NASH patients. Common genes for NAFLD progression were Chi3L1, ICAM1, MT1A, MT1H, ABCB11, ACOT1, CYP2C9, HSP90B1, and CPB2, which are involved in inflammation and oxidative stress pathways.

The present study investigated the shared vital genes and pathways between different stages of NAFLD, which may facilitate understanding NAFLD mechanisms and identifying potential therapeutic targets in this disease.