Hepatitis Monthly
Volume:24 Issue: 1, Dec 2024

 Macrophages play a significant role in both the development and regression of liver fibrosis, engaging in related pro-inflammatory and anti-inflammatory processes. In recent years, an increasing number of studies have elucidated the mechanisms by which macrophages influence liver fibrosis.

 This bibliometric analysis aims to investigate the research trends in liver fibrosis regulation by macrophages through a systematic literature review.

 We conducted a search for literature, including research articles and reviews, using the keywords 'liver fibrosis and macrophages' and 'liver cirrhosis and macrophages' in the Web of Science database, covering the period from 2007 to 2023. We retrieved and analyzed publications on liver fibrosis mediated by macrophages from the Web of Science Core Collection database on October 8, 2023. Visualization analysis was performed using CreateSpace (version 6.1.R6), VOSviewer (version 1.6.19), and Scimago Graphica (version 1.0.34.0).

 We identified a total of 1732 records in the WoSCC, of which 1664 papers were ultimately included in our analysis. China emerged as the country with the most significant number of publications, while Germany and the University of California San Diego stood out for their influence, with centralities of 0.41 and 0.14, respectively. Frank Tacke was identified as the most prolific author, contributing 49 papers. Hepatology was the journal with the highest number of publications and citations. The most frequently mentioned keywords in this field were liver fibrosis, expression, hepatic stellate cells, activation, inflammation, and macrophages.

 The study of macrophage-mediated liver fibrosis, particularly the mechanisms regulating the heterogeneity of hepatic macrophages, is a mature and promising research area. Macrophage-based therapies for liver fibrosis are anticipated to be crucial topics in the future. Bibliometric analysis offers valuable insights for future basic research directions and clinical practice.

 This study aimed to explore the effectiveness of endoscopic ultrasound elastography (EUS-EG) in evaluating liver fibrosis.

 The present study involved 11 patients with chronic liver disease who met study criteria and underwent EUS-EG, transabdominal ultrasound transient elastography (TUS-TE), and liver biopsy (LB) examinations at the same time. The Batts-Ludwig scoring system for liver fibrosis was used as the gold standard to analyze the correlation between the EUS-EG strain ratio (SR) and TUS-TE liver stiffness measurement with the pathological stage of liver fibrosis. The optimal cut-off value and area under the receiver operating characteristic curve (AUROC) of EUS-EG and TUS-TE for diagnosing liver fibrosis were calculated by drawing an ROC curve, and the corresponding sensitivity, specificity, and accuracy were also calculated.

 Endoscopic ultrasound elastography was highly positively correlated with the pathological stage of liver fibrosis (S ≥ 2, r = 0.759, P = 0.01), and TUS-TE was positively correlated with the pathological stage of liver fibrosis (S ≥ 2, r = 0.857, P = 0.003). The optimal diagnostic cut-off value of cirrhosis undergoing EUS-EG and TUS-TE was 0.84 and 14.2 Kpa, respectively. When the pathological stage was S0 - S1, the sensitivity, specificity, accuracy, and AUROC value of TUS-TE in the diagnosis of liver fibrosis were higher than those of EUS-EG (96.2%, 83.3%, 81.8%, and 0.96 vs. 94.6%, 75%, 72.7%, and 0.8958). When the pathological stage was ≥ S2, the sensitivity, specificity, accuracy, and AUROC values of EUS-EG were higher than those of TUS-TE (100%, 87.5%, 88.9%, and 0.97 vs. 100%, 83.3%, 88.9%, and 0.94).

 There is a superior correlation between EUS-EG combined with SR and the pathological stage of liver fibrosis, compared to TUS-TE, and it has the same or even higher diagnostic efficacy as TUS-TE. Larger prospective studies are needed to evaluate the clinical utility of this approach in the assessment of liver fibrosis.

Immune responses are pivotal in hepatitis B virus (HBV) infection, where Regulatory T cells (Treg) can contribute to sustaining the infection by suppressing immune responses. Forkhead box P3 (FoxP3) is the central regulator of Treg cells. In this case-control study, we investigated the role of FoxP3 -3279 (rs3761548) C/A polymorphism in the context of HBV infection. The study encompassed 140 healthy individuals as the control group and 70 individuals with chronic hepatitis B virus (CHBV) as the case group. The rs3761548 polymorphism was analyzed using the restriction fragment length polymorphism-PCR (PCR-RFLP) method. Furthermore, we evaluated FoxP3 gene expression in both HBV-positive and control groups using Real-Time PCR. The results revealed that the frequency of the AA genotype in the case and control groups was 52.9% and 44.3%, respectively, yielding an odds ratio (OR) of 1.411 with a 95% confidence interval (CI) ranging from 0.793 to 2.509. However, this difference did not achieve statistical significance (P = 0.242). Notably, the AC genotype was significantly more prevalent in the control group compared to the case group (P = 0.000). Moreover, FoxP3 gene expression was significantly higher in CHBV infection cases compared to the control group (P = 0.000). These findings suggest that the observed polymorphism may play a role in the pathogenesis and persistence of HBV infection. Nevertheless, further research is warranted to comprehensively investigate this phenomenon.

 Recent studies have suggested that polymorphisms in the Interleukin (IL)-6 gene promoter might be linked to chronic hepatitis C virus (HCV) infection, potentially affecting the infection's outcome.

 The purpose of this study was to determine whether the genetic variant of IL-6 gene polymorphisms (-174 G>C) is associated with HCV in patients compared to control subjects.

 Seventy-one patients infected with HCV and 79 healthy individuals referred to a hepatitis clinic in Mashhad, northeast Iran, were enrolled in the study. Blood samples were collected, and laboratory tests, including enzyme-linked immunosorbent assay (ELISA) for HCV antibodies and reverse transcription polymerase chain reaction (RT-PCR) for confirming HCV-positive results, were conducted. Genomic DNA was extracted from whole blood, and the ARMS-PCR method was used for genotyping the IL-6 gene polymorphisms (-174 G>C). Statistical analyses were performed using SPSS version 21 software.

 The C allele was found to be more frequent in HCV-infected patients compared to controls (P < 0.05; odds ratio [OR] = 2.91, 95% CI: 1.85 - 3.16), but this association was not significant after adjusting for confounders. Additionally, in a recessive model analysis (CC vs. GG + GC), the CC genotype was more prevalent among HCV-infected patients than in healthy individuals, though not significantly (P = 0.21; OR = 2.91, 95% CI: 0.55 - 15.53). The GG polymorphism was the most common genotype in both groups (P = 0.44), while the CC genotype was the least common (P = 0.12).

 The IL-6 gene polymorphism at this position may impart a certain level of risk for HCV infection, with carriers of the C allele potentially more susceptible to this infection. However, to further elucidate the role of this polymorphism in HCV, a larger cohort of HCV-infected patients and healthy individuals may be required.

 Hepatitis C and B virus infections significantly contribute to global chronic liver disease mortality.

 This study explores the role of serum markers (AST/ALT ratio, APRI Score, FIB-4 Score, and Forns index) in non-invasively assessing liver damage in patients with chronic hepatitis C and B.

 In this single-center, retrospective, observational study, we analyzed data from 327 patients to establish correlations between serological markers and fibrosis grade using Spearman's correlation. Receiver operator characteristic (ROC) analysis evaluated the ability of these markers to predict advanced fibrosis.

 In hepatitis B and C cohorts, all markers show significant positive correlations with liver fibrosis (P < 0.001). FIB-4 and the Forns index exhibit moderate correlation (Spearman’s rho 0.48), while AST/ALT and APRI score show mild correlation (Spearman’s rho 0.21 and 0.31). In hepatitis C, the Forns index (0.814) and FIB-4 (0.80) outperform other markers. In hepatitis B, Forns (AUC = 0.73), APRI (AUC = 0.68), and FIB-4 (AUC = 0.68) demonstrate significant predictive ability.

 FIB-4 and the Forns index hold clinical significance as fibrosis biomarkers in the management of chronic viral hepatitis. FIB-4 is a universal marker, while the interpretation of the Forns index requires consideration of the etiology of chronic viral hepatitis.

 In mid-2022, the World Health Organization (WHO) declared a moderate-risk outbreak due to an increase in severe acute hepatitis cases of unknown etiology in children. Several reports suggested a viral infection link, with the outbreak spanning over 35 countries. By June 2022, Mexico reported 69 probable cases across 5 entities to the WHO.

 A 4-year-old boy presented with vomiting, jaundice, choluria, and hepatomegaly. A multidisciplinary approach was employed, using an algorithm developed exclusively for clinical, epidemiological, and biochemical follow-up. Despite the negative identification of any associated microorganism and the absence of antibodies, liver function tests remained elevated. A fine needle liver biopsy was performed for diagnostic support, followed by histopathological study and sequencing and analysis of the complete high-depth transcriptome. Transcriptome analysis identified dysbiosis-related intestinal microbiota, including increased enterogenic and opportunistic pathogenic bacteria of the genus Clostridium, as well as HERV-K113, implicated in autoimmune disease development.

 The study's findings suggest possible immune-mediated mechanisms involving dysbiosis of the gut microbiota and the potential role of HERV-K113. Management and control of acute liver disease depend on specific causes, with the main challenge being early determination and implementation of optimal management strategies. The exact pathological mechanisms underlying pediatric acute hepatitis of unknown etiology remain elusive, warranting further studies to confirm or refute these hypotheses and elucidate the underlying pathological mechanisms

 A significant portion of individuals with hepatitis B virus (HBV) or hepatitis C virus (HCV) in the Netherlands remain undiagnosed, with a majority from migrant backgrounds.

 This study explored whether targeting HBV/HCV screening among individuals with metabolic risk factors enhances screening efficacy within a diverse ethnic cohort.

 Participants from six ethnic backgrounds were enlisted from the population-based, prospective HELIUS study in the Netherlands. Included were participants at elevated risk for non-alcoholic fatty liver disease (NAFLD), identified by elevated non-invasive tests (NITs) and/or metabolic risk factors, who were then tested for HBV/HCV. We evaluated screening efficiency, defined as the prevalence of HBV/HCV, by implementing two targeted screening strategies: (1) Testing individuals with elevated NITs; and (2) those with metabolic risk factors. These strategies were compared to a generic testing approach previously utilized in a subset of HELIUS participants. For non-Dutch origin participants, analyses were stratified based on the HBsAg-prevalence in their region of origin: Low (< 2%) and intermediate (2 - 8%).

 The study included 346 participants at risk for NAFLD, predominantly of Surinamese (n = 180; 45%), Dutch (n = 103; 26%), or Ghanaian (n = 63; 16%) origin. The generic testing approach encompassed 3,050 individuals. Among individuals from low and intermediate HBV-endemic countries, HBsAg-prevalence was 4.7% and 5.3% for those with elevated NITs, 3.9%, and 3.5% for those with metabolic risk factors, and 0.8% and 3.7% for generic testing, respectively. Regarding HCV, two individuals were anti-HCV-positive, with none being HCV-RNA-positive.

 Targeted screening based on metabolic risk factors or elevated NITs may be more efficient than generic screening among migrants from regions with low HBV prevalence.

 The epidemiology of cirrhosis, a significant public health issue, remains poorly understood in Iran.

 This study aimed to evaluate the characteristics, etiologies, complications, and outcomes of patients with cirrhosis who were registered in the Shiraz cirrhosis registry in Iran.

 In this descriptive-analytical study, a total of 2937 patients with cirrhosis from 2009 to 2016, and 683 patients from 2017 to 2022 were enrolled at Shahid Motahhari clinic in Shiraz and included in our database. Demographic, clinical, and laboratory data were collected at baseline and every six months thereafter. Mortality, hepatocellular carcinoma, and liver transplantation occurrences were monitored biannually. Statistical differences between groups were assessed using the Mann-Whitney U test, chi-square test, or Fisher's exact test, depending on the data distribution and the nature of the variables.

 The average age of patients during the first period was 47.4 ± 21.5 years, and for the second period, it was 54.8 ± 14.1 years. Biochemical levels and the prevalence of most complications were higher in the second period compared to the first. Ascites was the most common complication in the first group (52.1%), while esophageal varices were more prevalent in the second (40.1%). Hepatitis B and C were common among patients, especially in men. Patients registered in the earlier period had higher mortality and liver transplantation rates than those in the later period.

 The findings suggest that patients registered in the later period displayed better laboratory and clinical outcomes, likely due to improved management strategies over time. Viral hepatitis B and C were identified as the predominant etiologies among the patients with cirrhosis included in the study.

 In chronic hepatitis B (CHB) patients, hepatitis B surface antigen (HBsAg) seroclearance is the main target of therapy and is rarely observed.

 This study aimed to investigate the factors affecting HBsAg loss by focusing especially on the relationship between weight loss and HBsAg loss.

 This study was designed retrospectively to assess HBsAg status and clinical and laboratory findings in CHB patients, as well as cross-sectionally to evaluate lifestyle factors. A total of 5600 hepatitis B (HB) infection patients who were treated or followed between 2008 and 2020 were evaluated retrospectively. In the HBsAg loss group, 94 CHB patients were examined based on exclusion criteria, and 95 patients without HBsAg loss were matched as controls. Patient data and laboratory findings were retrieved from patient files. All participants were surveyed using a questionnaire developed by the authors, which inquired about the lifestyle characteristics of CHB patients. The questionnaire covered topics such as the use of herbal products, coffee consumption, medication history, antiviral treatment, concurrent diseases, weight changes, and patient demographics. Statistical analysis was performed using SPSS version 25.0. The Student's t-test was used to compare quantitative variables, while the chi-square test was used for categorical variables. A paired samples t-test was used to compare dependent samples. The statistical significance level was set at a p value less than 0.05.

 The basal mean hepatitis B virus (HBV) DNA level was significantly lower in the HBsAg loss group (P < 0.001). The prevalence of hyperlipidemia comorbidity (P = 0.008) and moderate/severe hepatosteatosis (P < 0.05) was significantly higher in the HBsAg loss group compared to the non-HBsAg loss group. Prior to HBsAg loss, 44 (47%) patients in the HBsAg loss group experienced weight loss, whereas only 22 (23%) patients in the non-HBsAg group had a history of weight loss (P < 0.001). Conversely, the incidence of weight gain was significantly lower in the HBsAg loss group (P = 0.001). A paired samples t-test was conducted to compare the baseline and last period body mass index (BMI) means of the HBsAg loss group, revealing a statistically significant decrease in mean BMI in the last period (P < 0.001).

 Weight loss was significantly associated with HBsAg seroclearance in patients with CHB infection. Conversely, weight gain was associated with HBsAg persistence.

 This study aimed to determine the cutoff value for diagnosis and predict mortality in hepatocellular carcinoma (HCC) based on serum total superoxide dismutase (SOD) activity.

 A retrospective case-control study of the SOD Model was conducted using data from a single-center dataset at Shandong Provincial Hospital Affiliated with Shandong First Medical University, China. Serum total SOD activity was analyzed in HCC patients (n = 124) and control subjects (n = 117). Receiver operating characteristic (ROC) curves were used to determine cutoff values of serum total SOD activity for HCC diagnosis. Overall survival (OS) was assessed using the Kaplan-Meier method.

 In the model groups, the cutoff level of total SOD activity for HCC was 169.2 U/mL (sensitivity: 87.23%, specificity: 91.95%), while for HCC [alpha fetoprotein (AFP) < 20 ng/mL], it was 173.4 U/mL (sensitivity: 86.79%, specificity: 88.51%). Additionally, in the validation groups, the true positive rate, true negative rate, and accuracy rate were all above 90%. Based on the cutoff value of SOD, HCC patients were assigned to an H-SOD and L-SOD group depending on their serum total SOD activity at admission before operation. The 5-year OS rate of the H-SOD group was 75.00%, and that of the L-SOD group was 36.59% in HCC patients (P = 0.0245). With a decrease in SOD activity, serum levels of Zn (t = 3.890, P = 0.0003) and Se (t = 7.694, P < 0.0001) were also significantly decreased and positively correlated with SOD activity (both P < 0.05) in HCC patients.

 Low serum total SOD activity may also be a risk factor for HCC. The decrease of SOD activity in HCC patients was partly related to a lack of Zn and Se.

Various weight loss surgeries exist, with no absolute superiority; each has pros and cons. Due to rising bariatric surgeries globally, it's vital to investigate comparisons between two-mini gastric bypass and Roux-en-Y gastric bypass (RYGB), especially regarding their impact on liver function.

The purpose of this study was to "draw comparisons between the effects of mini gastric bypass and laparoscopic Roux-en-Y gastric bypass on liver function at 6 months among patients with morbid obesity."

This cross-sectional study included 90 bariatric surgery candidates (Body Mass Index (BMI) 35 - 50) from 2018 - 2021. Forty-five had laparoscopic mini gastric bypass surgery, while 45 had Roux-en-Y gastric bypass. Demographic, anthropometric, lab, and sonographic tests were conducted at baseline, 3-, and 6-months post-surgery. Data was analyzed using SPSS.

In a study of 90 patients (75.6% female, mean age 38.6 ± 10.4 years), both surgeries (Mini gastric bypass (MGB) and RYGB) effectively reduced body weight, BMI, and waist circumference at 3- and 6-months post-surgery. However, MGB showed significantly higher BMI and weight loss compared to RYGB (P = 0.003). In 90 patients, both surgeries reduced weight and BMI. However, MGB showed better BMI/weight loss. LFTs (ALT, AST, ALP) remained stable after MGB but worsened at 3 months after RYGB before recovering by 6 months. Mini gastric bypass also showed better GGT improvement. Both procedures improved fatty liver grading, FBS, and HbA1C levels equally. No significant differences were observed in blood pressure, platelet count, hemoglobin, or MCV. Ferritin levels increased in both groups but were higher in RYGB. CRP was higher in RYGB at 3 months.

Roux-en-Y gastric bypass temporarily exacerbated liver enzymes and inflammation, but MGB resulted with more weight reduction. In comparison to RYGB, MGB improved LFTs more consistently.

Hepatic fibrosis is characterized by the increased proliferation and activation of hepatic stellate cells. Transforming growth factor-beta (TGF-β) stimulates these stellate cells, leading to the development of liver fibrosis. MicroRNA-146a and microRNA-29b have been identified as significant regulatory factors in fibrogenesis.

In this study, we investigated the ability of exosomes to alleviate liver fibrosis by enhancing the antifibrotic effects of miR-146a and miR-29b.

The LX-2 cells were exposed to TGF-β for 24 hours. Subsequently, the cells were treated with exosomes for an additional 24 hours. Following this treatment, the mRNA expression levels of alpha-smooth muscle actin (α-SMA), collagen1α, miR-146a, and miR-29b, as well as the protein levels of phosphorylated Smad3 (p-Smad3), were evaluated.

The findings revealed a significant elevation in the expression of α-SMA (5.37-fold, P < 0.0001) and collagen1α (3.87-fold, P < 0.001) genes, as well as an increase in the levels of p-Smad3 protein (5.87-fold, P < 0.0001) in the presence of TGF-β. Moreover, the expression of miR-146a (0.54-fold, P < 0.05) and miR-29b (0.46-fold, P < 0.01) genes exhibited a notable decrease compared to the control group under the influence of TGF-β. In our investigation, the administration of exosomes effectively mitigated the TGF-β-induced up-regulation of α-SMA (3.26-fold, P < 0.01) and collagen1α (1.76-fold, P < 0.01) genes, as well as the p-Smad3 protein (2.86-fold, P < 0.01), in LX-2 cells.

Our results suggest that exosomes effectively impede the continuous activation of hepatic stellate cells (HSCs) by enhancing the antifibrotic effects mediated by miR-146a and miR-29b. Moreover, exosomes demonstrate inhibitory effects on the TGF-β/Smad3 signaling pathway, resulting in decreased extracellular matrix (ECM) accumulation in the context of in vitro liver fibrosis.

This study aimed to explore the effectiveness of endoscopic ultrasound elastography (EUS-EG) in evaluating liver fibrosis.

The present study involved 11 patients with chronic liver disease who met study criteria and underwent EUS-EG, transabdominal ultrasound transient elastography (TUS-TE), and liver biopsy (LB) examinations at the same time. The Batts-Ludwig scoring system for liver fibrosis was used as the gold standard to analyze the correlation between the EUS-EG strain ratio (SR) and TUS-TE liver stiffness measurement with the pathological stage of liver fibrosis. The optimal cut-off value and area under the receiver operating characteristic curve (AUROC) of EUS-EG and TUS-TE for diagnosing liver fibrosis were calculated by drawing an ROC curve, and the corresponding sensitivity, specificity, and accuracy were also calculated.

Endoscopic ultrasound elastography was highly positively correlated with the pathological stage of liver fibrosis (S ≥ 2, r = 0.759, P = 0.01), and TUS-TE was positively correlated with the pathological stage of liver fibrosis (S ≥ 2, r = 0.857, P = 0.003). The optimal diagnostic cut-off value of cirrhosis undergoing EUS-EG and TUS-TE was 0.84 and 14.2 Kpa, respectively. When the pathological stage was S0 - S1, the sensitivity, specificity, accuracy, and AUROC value of TUS-TE in the diagnosis of liver fibrosis were higher than those of EUS-EG (96.2%, 83.3%, 81.8%, and 0.96 vs. 94.6%, 75%, 72.7%, and 0.8958). When the pathological stage was ≥ S2, the sensitivity, specificity, accuracy, and AUROC values of EUS-EG were higher than those of TUS-TE (100%, 87.5%, 88.9%, and 0.97 vs. 100%, 83.3%, 88.9%, and 0.94).

There is a superior correlation between EUS-EG combined with SR and the pathological stage of liver fibrosis, compared to TUS-TE, and it has the same or even higher diagnostic efficacy as TUS-TE. Larger prospective studies are needed to evaluate the clinical utility of this approach in the assessment of liver fibrosis.