Background: Affordable and effective diagnostic and treatment monitoring algorithms are urgently needed to achieve the global elimination of hepatitis C virus (HCV) infection. Methods: A total of 274 patients were treated with direct-acting antivirals (DAAs) in the Spanish Hospital of Albacete between 2004 and 2020. This study compared the enzyme-immunoassay technique for HCV core antigen (HCVcAg) with the determination of RNA of HCV (HCV RNA) by polymerase chain reaction (PCR) in monitoring treatment with DAA, setting the lower limit of detection of HCVcAg < 3 fmol/L and RNA < 10 IU/mL. In all cases, the P value of differences associated with the contrast test was less than or equal to 0.05. Results: We evaluated the viral loads of our patients before treatment, during their treatment, and after its completion. The HCV RNA quantification at diagnosis was 2309327 IU/mL. The mean HCVcAg load was 5972 fmol/L. There was a strong correlation between HCVcAg levels and RNA levels with a Spearman rho of 0.832 (P < 0.01). The HCVcAg sensitivity at diagnosis was 99%, but the specificity could not be calculated because there were no true negatives or false positives at this point. Twelve weeks after treatment, in patients with treatment failure, we obtained a mean of 19084 IU/mL for RNA, while for HCVcAg, the mean was 103 fmol/L. At this time point, we also found a strong correlation between HCVcAg levels and HCV RNA levels with a Spearman rho of 0.775 (P < 0.01). Finally, the virological cure was achieved in 99% of our patients. The results for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 100%, 99.87%, 86.33%, and 100%, respectively. Conclusions: HCVcAg determination is an excellent alternative to HCV RNA in the assessment of treatment response. This is particularly relevant in lower- and middle-income countries and resource-limited settings where the high cost of labor, equipment, and reagents can prohibit molecular testing.

Background: Accumulation of fat in the liver is one of the causes of non-alcoholic fatty liver disease (NAFLD), which affects about 30% of the world's population. Animal models have been useful tools for investigating the mechanisms involved in the etiology of NAFLD and developing new drugs. Objectives: This study aimed to present a new model for the detection of NAFLD in rats. Methods: Forty-eight rats were randomly divided into six experimental groups: (1) control; (2) 45% fructose + 35% olive oil + carbon tetrachloride (FFC1); (3) carbon tetrachloride (1: 4 in olive oil) (C1); (4) carbon tetrachloride (1: 6 in olive oil) (C2); (5) 12.5% fructose + 12.5% olive oil (FF); and (6) 20% fructose + carbon tetrachloride (1: 4 in olive oil) (FC1). Blood samples were taken in three steps, and liver tissue was dissected at the end of the sixth week for histopathological assessments. Results: After six weeks, the alanine transaminase (131.63 ± 1.51), aspartate transaminase (275 ± 1.0), and gamma-glutamyl transferase (4.30 ± 0.1) levels increased significantly in the C1 group (P < 0.05). The serum lipid profile showed significant changes in all groups compared to the controls (P < 0.01). According to the histological results, all experimental groups, except the C2 group, showed symptoms of NAFLD; nevertheless, a higher NAFLD Activity Score (NAS) was found in the C1 group, followed by the FC1 group, compared to the other groups. Conclusions: The present results revealed that injection of 0.1 mL/kg of carbon tetrachloride (C1 group), alone or along with a diet containing 20% fructose (FC1 group), provided useful animal models of NAFLD, although carbon tetrachloride injection alone is the most effective model in inducing NAFLD model that can be used as a new strategy in nutritional and pharmacological studies.

Background: Secreted frizzled-related protein 4 (sFRP4) is elevated in hepatocellular carcinoma (HCC) patients, suggesting that it can be served as a candidate marker for diagnosing HCC. However, little is known about its role in the different stages of chronic hepatitis B virus (HBV) infection. Objectives: This study was conducted to explore the clinical value of plasma sFRP4 in the different stages of chronic HBV infection. Methods: A total of 303 patients with chronic HBV infection were enrolled in this cross-sectional study. They were classified into the chronic hepatitis B (CHB), liver cirrhosis (LC), HCC, and acute-on-chronic liver failure (ACLF) groups on admission. Additionally, 30 healthy subjects were included in the healthy control (HC) group. The clinical value of plasma sFRP4 in the different stages of chronic HBV infection was analyzed. Results: There were 54, 85, 105, 59, and 30 cases in the CHB, LC, HCC, ACLF, and HC groups, respectively. ACLF group had the highest plasma sFRP4 levels compared to the CHB, LC, and HCC groups (all P < 0.001), followed by the HCC and LC groups. LC and HCC groups were found with up-regulated sFRP4 than the CHB group (all P < 0.05). High levels of plasma sFRP4 were recognized as an independent risk factor for distinguishing patients with ACLF from patients with CHB and LC [adjusted odds ratio (OR):1.005, 95% confidence interval (CI): 1.000 - 1.010, P = 0.043], with the area under the receiver operating characteristic curve (AUC) of 0.790 (95% CI: 0.726 - 0.844, P < 0.001). However, in patients with ACLF, plasma sFRP4 levels in the deteriorated group were higher than in the improved group, with a marginally significant difference (P = 0.071). The AUC for predicting the 90 days prognosis in patients with ACLF was 0.640 (P = 0.064). Conclusions: Plasma sFRP4 might be a biomarker to reflect the progression of chronic HBV infection. However, it was not significantly related to the prognosis in patients with ACLF; we did not find this, which may be due to the small sample size.

Background: Activation of hepatic stellate cells (HSCs) is an important driver of liver fibrosis, which is a health problem of global concern, and there is no effective solution for it at the present. Senescent activated HSCs are preferentially killed by natural killer cells (NK cells) to promote the regression of hepatic fibrosis. Objectives: The purpose of this study was to investigate the effect of polyinosinic-polycytidylic acid (poly I:C) on HSCs’ senescence, a trigger for NK cell-induced cytotoxicity. Methods: The senescence of HSCs was assessed by western blot, qRT-PCR, and flow cytometry, and NK cell cytotoxicity was assessed in a co-culture of NK cells with poly I:C-treated HSCs by measuring CD107a expression. Results: The expression of p16, p21, SA-β-gal, MICA/MICB, and ULBP2 increased in poly I:C-treated HSCs, rendering them significantly susceptible to NK cell cytotoxicity. Conclusions: Poly I:C induces cellular senescence in HSCs and triggers NK cell immunosurveillance, suggesting that the role of poly I:C in HSC senescence may promote fibrosis regression.

Background: Cytomegalovirus (CMV) is one of the leading viral agents that can pave the way for serious complications and organ damage in solid organ transplant (SOT) recipients after transplantation. Strategies have been developed to protect at-risk patients from CMV infection following transplantation. Since more than 90% of adults in Turkey were positive for CMV IgG, universal CMV prophylaxis was applied, and the results were evaluated. Objectives: This study aimed to evaluate the results of universal CMV prophylaxis after liver transplantation in the long term. Methods: A total of 1,090 liver transplant patients were evaluated in terms of CMV infection in the Organ Transplantation Institute of Inonu University, Malatya, Turkey, from October 2014 to December 2019. In order to identify the CMV infections, quantitative nucleic acid amplification (QNAT) was used to detect potential CMV DNA. The cut-off value of CMV DNA was determined to be 1000 copies/mL after transplantation. Results: According to the clinical and laboratory assessments, 33 (3%) patients were diagnosed with CMV infection, and 25 (2.3%) patients were evaluated as possibly having CMV syndrome. Also, eight of the 33 patients were assessed as having end-organ CMV disease and 25 as probable CMV syndrome. In the late period following prophylaxis, CMV infection was observed in 10 (0.9%) cases. The infection rate after prophylaxis (0.9%) was lower than the infection rate (2.1%) seen during prophylaxis. Conclusions: Close clinical follow-up with CMV prophylaxis and strict monitoring of CMV DNA by determining a specific cut-off point are important in the follow-up of liver transplant patients.

Background: A better understanding of the interaction between SARS-CoV-2 infection and HBV or HCV hepatitis is very important. Objectives: We aimed to determine the prevalence and the impact of pre-existing HBV and HCV infections in patients with COVID-19. Methods: We conducted a retrospective study and included all the subjects positive for SARS-CoV-2 from March to May 2020. We evaluated the prevalence of chronic HBV and HCV infections and performed a matched cohort analysis to compare COVID-19-related outcomes between patients with and without infections due to HBV or HCV. Results: Among 606 subjects, 12 cases (2%) had positive HBsAg, and 6 cases (0.99%) presented detectable HCV RNA. We recognized 80 individuals positive for SARS-CoV-2 with negative markers for HBV and HCV suitable for the matched analysis. No statistical differences in mechanical ventilation support and mortality rates were found (P = 0.27 and P = 0.80, respectively). Moreover, although not statistically different, individuals with viral hepatitis were more likely to be admitted to the Intensive Care Unit in comparison to those without HBV or HCV infections (29% vs. 15%). The median time of virus clearance was 27.5 days, with no difference between the two groups. Conclusions: In our cohort, the pre-existing viral liver infection did not have any impact on the clinical and virological evolution of COVID-19.

Objective: To assess the association between hepatic venous pressure gradient (HVPG) baseline and the response rate of cirrhotic in patients who received carvedilol treatment. Methods: In total 48 cirrhotic patients with a basic HVPG value greater than 12 mmHg were included (from July 2011 to October 2014). All patients received carvedilol treatment and underwent the second HVPG measurement 7 days later. In the following, all participants received an endoscopic variceal ligation (EVL) treatment. Results: HVPG was significantly reduced from 16.04 ± 3.10 to 12.76 ± 5.26 mmHg following carvedilol treatment. The response rate was about 58.33% (28/48). The response rate of the HVPG < 16 mmHg group (71.4%) was significantly higher than that of the HVPG ≥ 16 mmHg group (40%) (P < 0.05). Patients were followed up for a median of 26 months, ranged from 6 to 33 months. During the follow-up period (two years), the rebleeding rate was 9.97% and 49.56% in HVPG < 16 and HVPG ≥ 16 mmHg groups, respectively, with a statistically significant difference (P = 0.004). Also, the mortality rate (at 2 years) was 5.26% and 21.05%, respectively, which was significant (P = 0.035). Conclusions: This study demonstrated that the response rate of carvedilol on portal hypertension may be affected by the HVPG baseline, and the carvedilol was effective in reducing HVPG, especially for those with a HVPG < 16 mmHg.

peer reviewed

Background: Hepatitis C virus (HCV) is a major cause of liver diseases. Transmission of HCV, as a blood-borne virus, is a major concern for the safety of blood products. In Iran, intravenous drug abuse is a major risk factor for HCV transmission. Recently a change in the distribution of HCV genotype among Iranian blood donors has been reported, and genotype 3a is reported as the most frequent genotype. Also, genotype 3a is the dominant genotype among IDUs. Objective: To investigate the association between HCV genotype 3a circulating in the community, sequences of HCV genotype 3a were analyzed among different risk groups in Iran. Methods: In this cross-sectional study, a partial sequence of the NS5B region of the HCV genome was isolated from 58 blood donors, 48 intravenous drug users (IDUs), and 31 patients with inherited bleeding disorders (IBDs) infected with HCV genotype 3a were included. The published sequence data were obtained from the Gen Bank database and were compared to construct the phylogenetic trees. Results: Of 58 blood donors infected with subtype 3a, 31 (53.5%) reported the risk of intravenous drug abuse. In the phylogenetic tree, no separate cluster was formed to differentiate between HCV sequences in blood donors and IDUs. A cluster at the middle level was found in the phylogenetic tree formed by sequences from blood donors, IDUs, and patients with inherited bleeding disorders. Conclusions: The phylogenetic tree showed the phylogenetic mixing of genotype 3a sequences in BDs, IBD patients, and IDUs. The results confirmed the extensive transmission of IDU-related genotype 3a towards the general population.

Background: As obesity becomes more prevalent, non-alcoholic fatty liver disease (NAFLD) is also becoming a major worldwide health problem and the most common cause of chronic liver disease. A new obesity classification method based on a composite index which includes both the body mass index (BMI) and the waist-to-height ratio (WHtR) was recently proposed. However, the usefulness of this approach to assess the risk of NAFLD is unclear. Methods: This is a cross-sectional study of 1,276 adult individuals in Dalian, China. The Mann Whitney U test, χ2 test and t-test were used to compare differences between groups. Binary logistic regression analysis was used to identify independent risk factors. Based on BMI and WHtR tertiles, individuals were divided into five new groups. Spearman correlation and receiver operating characteristic curve (ROC) analyses were performed to compare the NAFLD risk factors among groups based on BMI alone, WHtR alone, or the combination of both indexes. Results: BMI, waistline circumference (WC), WHtR, alanine aminotransferase (ALT), weight, triglycerides (TG), γ-glutamyl transpeptidase (GGT), serum uric acid (SUA), red blood cell (RBC) counts, hemoglobin levels (HGB), fasting blood glucose (FBG) and aspartate aminotransferase (AST) levels were identified as high risk factors for NAFLD (all AUC > 0.7). Logistic regression analysis suggested that BMI and WHtR were independent predictors of the appearance of NAFLD (the ORs for BMI and WHtR were 1.595 and 4.060E-11, respectively; all P < 0.001). The combination of BMI and WHtR tertiles significantly improved the correlation coefficient and Area under the receiver operating characteristic curve (AUC) for NAFLD risk factors in subjects classified as overweight or obese when compared with either BMI or WHtR alone. Conclusions: BMI, WC, WHtR, ALT, weight, TG, GGT, SUA, RBC, HGB, FBG, AST were high risk factors for NAFLD. The composite BMI and WHtR index improved body fat classification and the ability to detect individuals with NAFLD risk, offering a more precise method for the early identification of high- and low-risk NAFLD patients.