Liver Damage In Chronic Hepatitis Research Articles

POLYMORPHISM OF INTERLEUKIN-10 (-819) GENE IS NOT ASSOCIATED WITH LIVER DAMAGE AMONG CHRONIC HEPATITIS B PATIENTS

Introduction: Chronic hepatitis B (CHB) is characterized by chronic liver inflammation and hepatocellular damage caused by hepatitis B virus (HBV), leading to fatal liver diseases such as cirrhosis and hepatocellular carcinoma (HCC). Liver damage causes elevated levels of serum alanine aminotransferase (ALT). Previous studies have shown that IL-10 gene polymorphism (-819 C/T) is linked to several diseases, including inflammatory, autoimmune diseases, and cancer. Purpose: To investigate the relationship between IL-10 gene polymorphisms (-819 C/T) and liver damages in chronic hepatitis B patients at Arifin Achmad Regional Hospital, Riau Province. Method: This study was an analytical study with a cross-sectional approach. Liver damages were examined by measuring ALT levels, and IL-10 gene polymorphisms were analyzed using Amplification-Refractory Mutation System Polymerase Chain Reaction (ARMS-PCR). Results: There were 74 subjects included in this study, aged 45.47±13.42 years old, consisting of 43 males (58.1%) and 31 females (41.9%). Of 74 subjects, 35 CHB patients were presented without complication, 26 CHB patients were complicated with cirrhosis, and 13 CHB patients were complicated with hepatoma. The genotype of the IL-10 (-819) gene polymorphism in this study was found as follows: CT genotype in 34 subjects (45.9%), TT genotype in 30 subjects (40.5%), and CC genotype in 10 subjects (13.5%). There was no significant relationship between IL-10 gene polymorphisms (- 819) and liver damage in chronic hepatitis B patients (p> 0.05). Conclusion: IL-10 gene polymorphism (-819) may not contribute to liver damages among CHB patients.

Systematic review and Meta-analysis of efficacy and safety of Compound Glycyrrhizin Injection in improving chronic hepatitis B liver damage

To evaluate the efficacy and safety of Compound Glycyrrhizin Injection(CGI) in improving liver damage in chronic hepatitis B(CHB). PubMed, Web of Science, SinoMed, CNKI, Wanfang and VIP databases were retrieved from their inception to February 10, 2020. The randomized controlled trial(RCT) of CGI in the treatment of CHB was included. Data were independently extracted by two authors, and the methodological quality was evaluated using the Cochrane bias risk assessment tool by other two authors. Statistical analysis was performed using RevMan 5.3 software. A total of 18 two-armed RCTs were included, involving 1 915 participants. The methodological quality of all studies included was generally low. In the comparison between CGI and diammonium glycyrrhizinate, the results showed that CGI was superior to the control group in improving the overall clinical effectiveness, but there was no statistical difference between the two groups in increasing ALT normalization rate, reducing ALT and AST level. In the comparison between CGI and diammonium glycyrrhizinate+other general hepatoprotective drugs, the results showed that CGI was superior to the control group in reducing AST level, while there was no statistical difference between the two groups in reducing ALT level and increasing overall clinical effectiveness. In the comparison between CGI+other commonly used drugs(including energy mixture, glutathione, vitamins, potassium magnesium aspartate) and diammonium glycyrrhizinate+other commonly used drugs, the results showed that CGI combined with other commonly used drugs was better than the control group in reducing ALT and AST level and improving the clinical total effective rate, and there was no statistical difference between the two groups in increasing the rate of ALT normalization. In the comparison between CGI+other commonly used drugs and other commonly used drugs, the results showed that CGI combined with other commonly used drugs was superior to the control group in reducing ALT and AST level and improving the overall clinical effectiveness. In the comparison between CGI+vitamins and diammonium glycyrrhizinate+potassium magnesium aspartate+vitamins, the results showed no statistical difference between the two groups in reducing AST level. A small number of studies included reported that CGI caused mild adverse reactions when used alone or in combination with other drugs. Based on the results, CGI has a certain effect in improving CHB liver damage, but the evidence is not enough to prove that CGI would cause serious adverse events. In the future, more well-designed and strictly-enforced RCT with an adequate sample size are needed to further evaluate the effect CGI in alleviating CHB liver damage.

Procoagulant imbalance influences cardiovascular and liver damage in chronic hepatitis C independently of steatosis.

Patients with chronic HCV infection besides hepatitis often present cardiovascular damage, the pathogenesis of which is not defined. In chronic liver diseases, including NAFLD and cirrhosis, a procoagulant imbalance, potentially responsible for atherosclerosis has been reported. We aimed at evaluating whether a procoagulant imbalance is present also in non-cirrhotic patients with HCV infection and whether the procoagulant imbalance correlates with cardiovascular damage. The correlation between the procoagulant imbalance, coexisting steatosis, and liver fibrosis was analysed. From 2014 to 2018, 393 subjects (205 patients with chronic HCV infection from two liver units and 188 controls) were enrolled. Metabolic, cardiovascular, liver assessment and coagulation parameters-procoagulants (FII and FVIII) and anticoagulants (antithrombin and protein C [PC]), endogenous thrombin potential (ETP), peak-thrombin and their ratios (with/without thrombomodulin)-were determined. The procoagulant imbalance (defined as high FVIII, FVIII/PC ratio, ETP-ratio and peak-thrombin-ratio (with/without thrombomodulin)) was significantly higher in patients with chronic HCV than controls. Steatosis was detected in 87 patients (42%). No difference in coagulation imbalance, carotid and cardiac parameters and severity of liver fibrosis was observed in patients with or without steatosis, despite the latter had less severe metabolic alterations. The FVIII/PC ratio was independently associated with carotid intima-media thickness (coefficient 0.04, 95% CI 0.002-0.07, P=.04) and liver fibrosis (coefficient 0.64, 95% CI 0.37-0.92, P<.0001). Patients with HCV infection, even in the absence of cirrhosis have a procoagulant-imbalance that possibly plays a role in increasing the risk of cardiovascular disease and progression of fibrosis.

Comparison of non-invasive models for predicting liver damage in chronic hepatitis B patients

Inexpensive blood tests have been well established as alternatives to liver biopsies to evaluate liver fibrosis in CHB patients. Here, we aim to compare their diagnostic accuracy in assessing liver fibrosis and necroinflammation. A retrospective study was performed to evaluate the predictive value of non-invasive models in chronic hepatitis B patients with liver fibrosis by the area under receiver operating characteristic curve (AUROC). The clinical data of 160 patients were collected from medical records. Of the 160 consecutive treatment-naïve CHB patients, 29 (16%) had significant fibrosis and 34 (21%) had severe necroinflammation. The AUROC of the gamma-glutamyl transpeptidase to platelet ratio (GPR) (0.761, 95% CI 0.671–0.850) for predicting significant fibrosis was significantly higher than that of the aspartate transaminase-to-platelet ratio index (APRI) (0.680, 95% CI 0.585–0.774, p = 0.034), but comparable with the fibrosis index based on four factors (Fib-4) (0.746, 95% CI 0.656–0.836, p = 0.703), while for predicting severe necroinflammation, the performance of the GPR (AUROC = 0.869, 95% CI 0.800–0.937) was better than the APRI (AUROC = 0.816, 95% CI 0.740–0.892, p = 0.085) and Fib-4 (0.792, 95% CI 0.711–0.873, p = 0.023). GPR is a satisfactory model to stage liver fibrosis and to grade necroinflammation activity, representing a convenient non-invasive alternative to liver biopsy in China. los análisis de sangre asequibles se han consolidado como alternativas a la biopsia hepática para evaluar la fibrosis hepática en pacientes con HBC. En este caso, nuestro objetivo es comparar su precisión diagnóstica en la evaluación de la fibrosis hepática y en la necroinflamación. se realizó un estudio retrospectivo para evaluar el valor pronóstico de los modelos no invasivos en pacientes con hepatitis B crónica con fibrosis hepática en el área bajo la curva de rendimiento diagnóstico (AUROC). Se recopilaron los datos clínicos de 160 pacientes a partir de las historias clínicas. De 160 pacientes HBC que no habían recibido tratamiento consecutivo, 29 (16%) presentaron una importante fibrosis y 34 (21%), necroinflamación grave. La AUROC de la gammaglutamiltranspeptidasa respecto a la proporción de plaquetas (GPR) (0,761; IC95%: 0,671-0,850) para pronosticar una fibrosis importante fue considerablemente más alta que el índice de relación aspartato-transaminasa-plaquetas (APRI) (0,680; IC95%: 0,585-0,774; p = 0,034), pero comparable con el índice de fibrosis basado en cuatro factores (Fib-4) (0,746; IC95%: 0,656-0,836; p = 0,703), mientras que para el pronóstico de la necroinflamación grave, el rendimiento de GPR (AUROC = 0,869; IC95%: 0,800-0,937) fue mejor que el de APRI (AUROC = 0,816; IC95%: 0,740-0,892; p = 0,085) y el de Fib-4 (0,792; IC95%: 0,711-0,873; p = 0,023). el GPR es un modelo satisfactorio para clasificar la fibrosis hepática y para calificar la actividad de la necroinflamación, y representa una alternativa práctica y no invasiva a la biopsia hepática en China.

Comparison of non-invasive models for predicting liver damage in chronic hepatitis B patients

IntroductionInexpensive blood tests have been well established as alternatives to liver biopsies to evaluate liver fibrosis in CHB patients. Here, we aim to compare their diagnostic accuracy in assessing liver fibrosis and necroinflammation. Patients and methodsA retrospective study was performed to evaluate the predictive value of non-invasive models in chronic hepatitis B patients with liver fibrosis by the area under receiver operating characteristic curve (AUROC). The clinical data of 160 patients were collected from medical records. ResultsOf the 160 consecutive treatment-naïve CHB patients, 29 (16%) had significant fibrosis and 34 (21%) had severe necroinflammation. The AUROC of the gamma-glutamyl transpeptidase to platelet ratio (GPR) (0.761, 95% CI 0.671–0.850) for predicting significant fibrosis was significantly higher than that of the aspartate transaminase-to-platelet ratio index (APRI) (0.680, 95% CI 0.585–0.774, p=0.034), but comparable with the fibrosis index based on four factors (Fib-4) (0.746, 95% CI 0.656–0.836, p=0.703), while for predicting severe necroinflammation, the performance of the GPR (AUROC=0.869, 95% CI 0.800–0.937) was better than the APRI (AUROC=0.816, 95% CI 0.740–0.892, p=0.085) and Fib-4 (0.792, 95% CI 0.711–0.873, p=0.023). DiscussionGPR is a satisfactory model to stage liver fibrosis and to grade necroinflammation activity, representing a convenient non-invasive alternative to liver biopsy in China.

IgG Antibodies to GlcNAcβ and Asialo-GM2 (GA2) Glycans as Potential Markers of Liver Damage in Chronic Hepatitis C and the Efficacy of Antiviral Treatment.

Total serum IgG level is a surrogate marker of hepatitis C (HC) severity. Antibodies (Abs) to microbial glycans could be markers of HC severity caused by the translocation of microbial products. The level of anti-glycan (AG) Abs was analysed in serum samples of patients (n = 128) with chronic HC in ELISA using fourteen synthetic glycans present in microbes and adhesins to evaluate the association of Abs with clinical parameters and the efficacy of antiviral treatment. The anti-GlcNAcβ IgG level was significantly higher in patients with fibrosis (P = 0.021) and severe portal inflammation (P < 0.001) regardless of other clinical parameters. The ROC curve analysis showed sensitivity of 0.59, specificity of 0.84, and AUC of 0.71 in discriminating F0 from F1–4 (HCV genotype-1b-infected patients). The level of anti-GA2 Abs before Peg-IFN/RBV treatment was significantly higher in nonsustained viral response (non-SVR) to treatment than in SVR (P = 0.033). ROC analysis showed sensitivity of 0.62, specificity of 0.70, and AUC of 64. Correlations of AG Abs to clinical parameters were found. The quantification of anti-GlcNAcβ Abs deserves attention in assessment of the hepatic damage while anti-GA2 Abs may be a sign of immune response related to the antiviral treatment.

Estimation of Serum Interleukin-18 and Hs-CRP in Chronic Hepatitis C Infected Patients at Assuit Governorate, Egypt

Hepatitis C virus (HCV) infection is a global health problem. Egypt has the highest prevalence of hepatitis C virus (HCV) in the world. Interleukin-18 (IL-18) as a critical multipotent inducer of innate and acquired immune responses. This study aimed to estimate IL-18 and hs-CRP levels in patients at different stages of chronic HCV infection and to evaluate IL-18 as a non-invasive marker of the severity of liver damage in chronic hepatitis C patients, and to investigate the characteristics of hs-CRP and its correlation to chronic HCV infection. This study included 50 chronic HCV patients and 20 healthy. They were subjected to history taking, liver function tests, real-time PCR test and other laboratory tests. Serum IL-18 levels were assayed by an enzyme-linked immunosorbent assay. Our study was conducted on 70 subjects with their ages ranging between 9-70 years. 50 HCV chronically infected patients, were 42 (84.0%) males and 8 (16.0%) female. Twenty apparent healthy individuals without HCV infection used as a control, they were 18 (90%) males and 2 (10%) females. Serum IL-18 and Hs-CRP levels were higher in chronic HCV patients compared to healthy. Responders to interferon treatment had higher interleukin-18 levels than non-responders. However, Serum Hs-CRP were higher in non-responders than Responders to interferon treatment. Patients with hepatocellular carcinoma had higher interleukin-18 and Hs-CRP levels than those without hepatocellular carcinoma. Serum IL-18 could be a significant predictor for the severity of HCV infection and monitoring of therapy response in chronic HCV patients with other tests.

Prostaglandin E2 facilitates Hepatitis B virus replication by impairing CTL function

Reversal of T cell dysfunction is a novel and promising approach for the treatment of chronic diseases. PGE2, one of most studied Prostaglandins, exhibits strong and versatile immunoregulation activity on different immune cells including T cells, and has become a promising therapeutic target. Here we found that compared to healthy donors, patients with chronic Hepatitis B virus (HBV) infection had significantly elevated serum PGE2 level. Importantly, serum PGE2 concentration correlated with viral load and liver damage in Chronic hepatitis B(CHB)patients. In AAV-HBV1.2 mouse model, administration of PGE2 analogue promoted HBV replication, while antagonists for EP2 and EP4, two important receptors for PGE2, inhibited virus replication. However, PGE2 analogue had no significant effect on the growth and virus replication in cultured HBV-harboring hepatocyte cell line. Further analysis showed that high PGE2 level in CHB patients correlated with high Tim-3 expression and low level of perforin and granzme B in CD8 + T cells. In parallel, blockade of PGE2 signaling restored the function of CD8 + T cells and controls HBV infection. Depletion of CD8 + T cells almost abrogated the effects of PGE2 on HBV replication. These findings identify PGE2 as a negative regulator for CD8 + T cells contributing to HBV persistence and the intervention of PGE2 signaling might be of potentially translational significance.

The interplay between intrahepatic lymphocyte populations and Hepatitis B virus antigens related to liver damage in chronic hepatitis

Background: Chronic hepatitis B virus (HBV) infection is still a global health problem. Even though it is well known that adaptative immune response plays an important role in the pathogenesis of chronic infection, the impact of each immune cell population in liver damage and viral surveillance is still a matter of debate. Our aim was to elucidate the interplay between the immune response and viral activity in the context of liver damage. Methods & Materials: Immunostaining was performed in 23 liver biopsies from CHB treatment naïve patients (40% HBeAg-positive) to:1) characterize liver infiltrate [Th (CD4+), Th1 (Tbet+), Th17 (IL-17A+), Treg (Foxp3+), and CTL (CD8+)] [portal quantification: immunostained/total lymphocytes; lobular quantification: immunostained lymphocytes in 10 fields; (400x)], 2) evaluate the Hepatitis B surface antigen (HBsAg) expression (presence was determined). Inflammatory activity and fibrosis were assessed using the modified Knodell scoring system (Histological Activity Index, HAI) and METAVIR. Results: All studied populations were observed in portal/periportal infiltrates with predominance of Th {Th [0.65 (0.33-0.77)] > CTL [0.54 (0.16-0.74)] > Treg [0.09 (0.00-0.25)] > Th1 [0.07 (0-0.20)] > Th17 [0.05 (0-0.20)]}. However, only CTL were present in the intralobular area [2.77 (0.01-0.25)]. Concerning liver damage, Th17 frequency was increased in cases with more severe fibrosis (p = 0.04), while Th in cases with severe hepatitis (p = 0.02) mostly due to Treg (p = 0.02). The frequency of intralobular CTL also depicted association with severe hepatitis (p = 0.02). Regarding HBV antigen profile, only 62% of cases showed presence of HBsAg, being its absence associated with a higher number of Treg (p = 0.02) and severe hepatitis (p = 0.01). Moreover, HBe Ag-positive cases exhibited higher Treg and Th frequencies (p = 0.0002 and p = 0.037; respectively). Conclusion: Although Treg population was highly represented in the infiltrate, they were not related to liver damage. In contrast, intrahepatic Th17 mediated fibrosis severity. The presence of CTL in the intralobular area may indicate a relationship between them and hepatocytes denoting their contribution to hepatitis severity. Finally, our results suggest that the presence of a regulatory microenvironment enhances viral replication. This hypothesis is supported by the fact that a higher Treg frequency was observed in the context of absence HBsAg as well as among HBeAg-positive cases.

Role of osteoprotegerin/receptor activator of nuclear factor kappa B/receptor activator of nuclear factor kappa B ligand axis in nonalcoholic fatty liver disease.

Concomitantly with the increase in the prevalences of overweight/obesity, nonalcoholic fatty liver disease (NAFLD) has worldwide become the main cause of chronic liver disease in both adults and children. Patients with fatty liver display features of metabolic syndrome (MetS), like insulin resistance (IR), glucose intolerance, hypertension and dyslipidemia. Recently, epidemiological studies have linked obesity, MetS, and NAFLD to decreased bone mineral density and osteoporosis, highlighting an intricate interplay among bone, adipose tissue, and liver. Osteoprotegerin (OPG), an important symbol of the receptor activator of nuclear factor-B ligand/receptor activator of nuclear factor kappa B/OPG system activation, typically considered for its role in bone metabolism, may also play critical roles in the initiation and perpetuation of obesity-related comorbidities. Clinical data have indicated that OPG concentrations are associated with hypertension, left ventricular hypertrophy, vascular calcification, endothelial dysfunction, and severity of liver damage in chronic hepatitis C. Nonetheless, the relationship between circulating OPG and IR as a key feature of MetS as well as between OPG and NAFLD remains uncertain. Thus, the aims of the present review are to provide the existent knowledge on these associations and to discuss briefly the underlying mechanisms linking OPG and NAFLD.

Unique Characteristics Associated with Sustained Liver Damage in Chronic Hepatitis C Patients Treated with Direct Acting Antivirals

Background and Aims: Direct-acting antivirals (DAAs) dramatically improve the sustained virological response (SVR) of chronic hepatitis C (CHC) patients. However, continuous liver damage after SVR may be a risk of hepatocellular carcinoma (HCC). We clarified pretreatment characteristics related to sustained liver damage after SVR. Methods: A total of 286 CHC patients were treated with an interferon-free DAA regimen. Among them, 250 patients achieved SVR for 12 weeks after the end of treatment (SVR12); these individuals were classified based on α-fetoprotein (AFP) and alanine transaminase (ALT) levels posttreatment. Baseline characteristics significantly associated with AFP >5 ng/mL and ALT level ≥20 IU/L after SVR were clarified using multivariate analyses. Results: Among the pretreatment factors examined, serum AFP values and the presence of fatty liver (FL) were significantly associated with abnormal AFP (p < 0.0001) and ALT levels 12 weeks after SVR12 (SVR24; p = 0.0109). For 126 patients who showed an increase in baseline AFP level, FL, fibrosis-4 (FIB-4) index, and albumin levels before treatment were related to abnormal AFP at SVR24 (p = 0.0005, 0.0232, and 0.0400 for FL, FIB-4 index, and albumin, respectively). Similarly, for 150 patients with abnormal baseline ALT levels, FL was associated with an ALT level ≥ 30 IU/L after SVR (p = 0.0430). Conclusions: High FIB-4 index, low albumin level, and FL before DAA treatment were associated with a risk of sustained liver damage with AFP and ALT elevation after SVR; patients with these factors should be carefully monitored for emergence of HCC.

NK cells lacking FcεRIγ are associated with reduced liver damage in chronic hepatitis C virus infection.

A novel subset of human natural killer (NK) cells, which displays potent and broad antiviral responsiveness in concert with virus-specific antibodies, was recently uncovered in cytomegalovirus (CMV)+ individuals. This NK-cell subset (g-NK) was characterized by a deficiency in the expression of FcεRIγ adaptor protein and the long-lasting memory-like NK-cell phenotype, suggesting a role in chronic infections. This study investigates whether the g-NK-cell subset is associated with the magnitude of liver disease during chronic hepatitis C virus (HCV) infection. Analysis of g-NK-cell proportions and function in the PBMCs of healthy controls and chronic HCV subjects showed that chronic HCV subjects had slightly lower proportions of the g-NK-cell subset having similarly enhanced antibody-dependent cellular cytotoxicity responses compared to conventional NK cells. Notably, among CMV+ chronic HCV patients, lower levels of liver enzymes and fibrosis were found in those possessing g-NK cells. g-NK cells were predominant among the CD56(neg) NK cell population often found in chronic HCV patients, suggesting their involvement in immune response during HCV infection. For the first time, our findings indicate that the presence of the g-NK cells in CMV+ individuals is associated with amelioration of liver disease in chronic HCV infection, suggesting the beneficial roles of g-NK cells during a chronic infection.

Transmembrane 6 superfamily member 2 gene E167K variant impacts on steatosis and liver damage in chronic hepatitis C patients.

Steatosis and inherited host factors influence liver damage progression in chronic hepatitis C (CHC). The transmembrane 6 superfamily member 2 (TM6SF2) gene E167K variant increases liver fat and risk of progressive steatohepatitis by interfering with lipoprotein secretion. Our aim was to determine whether the E167K variant affects histological severity of steatosis, necroinflammation, and fibrosis in a cross-sectional cohort of 815 Italian therapy-naïve CHC patients. The association with clinically significant fibrosis was replicated in 645 Swiss/German patients. The TM6SF2 E167K variant was genotyped by TaqMan assays, steatosis graded according to the nonalcoholic fatty liver disease activity score, and necroinflammation and fibrosis graded and staged according to Ishak in Italian, and to Metavir in Swiss/German patients. The E167K variant was detected in 69 (9%) Italian patients and was associated with more severe steatosis, independently of confounders (P = 0.038). The association between E167K and steatosis severity was present in patients not infected by genotype 3 (G3) HCV (P = 0.031), but not in those infected by G3 HCV (P = 0.58). Furthermore, the E167K variant was associated with more severe necroinflammation (Ishak grade; adjusted P = 0.037) and nearly associated with more severe fibrosis (Ishak stage; adjusted P = 0.058). At multivariate logistic regression analysis, the E167K variant was independently associated with histologically probable or definite cirrhosis (Ishak stage S6; odds ratio [OR]: 2.19; 95% confidence interval [CI]: 1.18-3.93; P = 0.010). After further conditioning for steatosis and necroinflammation, the E167K variant remained associated with cirrhosis (OR, 3.15; 95% CI: 1.60-5.99; P < 0.001). In Swiss/German patients, the E167K variant was independently associated with clinically significant fibrosis Metavir stage F2-F4 (OR, 1.81; 95% CI: 1.12-3.02; P = 0.016). TM6SF2 E167K variant impacts on steatosis severity and is associated with liver damage and fibrosis in patients with CHC.

Distinctive intrahepatic characteristics of paediatric and adult pathogenesis of chronic hepatitis C infection

Mechanisms leading to liver damage in chronic hepatitis C (CHC) are being discussed, but both the immune system and the virus are involved. The aim of this study was to evaluate intrahepatic viral infection, apoptosis and portal and periportal/interface infiltrate in paediatric and adult patients to elucidate the pathogenesis of chronic hepatitis C. HCV-infected, activated caspase-3+ and TUNEL+ hepatocytes, as well as total, CD4+, CD8+, Foxp3+ and CD20+ lymphocytes infiltrating portal and periportal/interface tracts were evaluated in 27 paediatric and 32 adult liver samples by immunohistochemistry or immunofluorescence. The number of infected hepatocytes was higher in paediatric than in adult samples (p 0.0078). In children, they correlated with apoptotic hepatocytes (activated caspase-3+r = 0.74, p < 0.0001; TUNEL+r = 0.606, p 0.0017). Also, infected (p = 0.026) and apoptotic hepatocytes (p = 0.03) were associated with the severity of fibrosis. In adults, activated caspase-3+ cell count was increased in severe hepatitis (p = 0.009). Total, CD4+, CD8+ and Foxp3+ lymphocyte count was higher in adult samples (p < 0.05). Paediatric CD8+ cells correlated with infected (r = 0.495, p 0.04) and TUNEL+ hepatocytes (r = 0.474, p = 0.047), while adult ones correlated with activated caspase-3+ hepatocytes (r = 0.387, p 0.04). In adults, CD8+ was associated with hepatitis severity (p < 0.0001) and correlated with inflammatory activity (CD8+ r = 0.639, p 0.0003). HCV, apoptosis and immune response proved to be involved in CHC pathogenesis of both paediatric and adult patients. However, liver injury in paediatric CHC would be largely associated with a viral cytopathic effect mediated by apoptosis, while in adults it would be mainly associated with an exacerbated immune response.

Regulatory Role of CD4+CD25+Foxp3+ Regulatory T Cells on IL-17-Secreting T Cells in Chronic Hepatitis B Patients

Both interleukin (IL)-17-secreting CD4(+) T (Th17) and CD4(+)CD25(+)Foxp3(+) T regulatory (Treg) cells have been shown to be associated with disease progression or liver damage in chronic hepatitis B (CHB) patients. However, the relationship between Treg cells and IL-17-secreting T cells in hepatitis B virus (HBV) infections is unclear. The frequencies of Treg cells and IL-17-secreting T cells in hepatitis B e antigen (HBeAg)-positive CHB patients and healthy subjects were measured by flow cytometric analysis. The role of Treg cells on the differentiation of Ag-specific IL-17-secreting T cells was determined by removing the Treg cells from peripheral blood mononuclear cells (PBMCs) in HBeAg-positive CHB patients. The frequencies of both Th17 (1.71 ± 0.58 vs. 1.08 ± 0.36 %; P < 0.01) and Treg cells (8.92 ± 4.11 vs. 6.45 ± 1.56 %; P < 0.01) were increased in the peripheral blood of HBeAg-positive CHB patients compared with healthy controls, but in not the IL-17-secreting CD8(+) T (Tc17) cells. The frequency of Treg cells was significantly associated with that of Th17 cells (r = 0.625, P = 0.001) in CHB patients. Spearman analysis showed a positive correlation between the frequency of Treg cells and HBV DNA load (r = 0.508, P = 0.008), as well as between the frequency of Th17 cells and serum alanine aminotransferase level (r = 0.516, P = 0.007). The deletion of Treg cells significantly enhanced both Th17 and Tc17 cell development in PBMCs following recombinant HBV core antigen stimulation. Our data indicate a clear inverse relationship between Th17 cells and Treg cells and that Treg cells can inhibit Th17 cell development in CHB patients.

Elevated Alpha Fetoprotein in Chronic HCV Liver Disease with and without Hepatocellular Carcinoma in Egyptian Patients

This work to determine the relation of serum Alpha fetoprotein (AFP) elevated values and liver damage in chronic Hepatitis C Virus (HCV) infected patients with and without cirrhosis ( compensated and decompensated ) . A cross-sectional descriptive study was done at National liver institute in Egypt from the period of January 2014 till june 2014 Patients enrolled in study were known cases of chronic Hepatitis C Virus liver disease and were complicated by development of cirrhosis and hepatocellular carcinoma . Demographic data such as age and gender were recorded. Detailed clinical history and examination were carried out and recorded. Complete blood count , liver function test, total protein, Albumin/Globulin (A/G) ratio, serum Albumin, HBsAg, anti HCV, ultrasound whole abdomen and CT scan Abdomen . Alpha fetoprotein were investigated in ninety HCV infected patients classify into three group ; group I without cirrhosis and without ascitis , group II with cirrhosis and with ascitis , group III Hepatocellular carcinoma with cirrhosis and with ascitis . Elevation level of alpha fetoprotein in all patients but in different degree .the mean in group 1 (5.3 ng/dl), in group 2 (33.4 ng/dl) and in group 3 (457.4 ng/dl) which is markedly elevated. There was a significant differencebetween serum alpha fetoprotein level in Hepatitis C Virus infected patients with and without cirrhosis and those with hepatocelleular carcinoma. The cut off level of >400 ng/dl is considered to be the most sensitive level for detection of hepatocellular carcinoma (93.3%) . This study suggests that serum alpha fetoprotein has significant association with liver damage . The level of alpha fetoprotein may serve as a useful sensitive marker for detection of hepatocellular carcinoma especially at level higher than 400 ng/dl and to differentiate between chronic HCV without cirrhosis and without ascitis and between HCV with cirrhosis and with ascitis . Alpha fetoprotein may serve as useful marker for follow up the progression of liver damage .

Serum Apoptosis Markers Related to Liver Damage in Chronic Hepatitis C: sFas as a Marker of Advanced Fibrosis in Children and Adults While M30 of Severe Steatosis Only in Children

BackgroundLiver biopsy represents the gold standard for evaluating damage and progression in patients with chronic hepatitis C (CHC); however, developing noninvasive tests that can predict liver injury represents a growing medical need. Considering that hepatocyte apoptosis plays a role in CHC pathogenesis; the aim of our study was to evaluate the presence of different apoptosis markers that correlate with liver injury in a cohort of pediatric and adult patients with CHC.MethodsLiver biopsies and concomitant serum samples from 22 pediatric and 22 adult patients with CHC were analyzed. Histological parameters were evaluated. In serum samples soluble Fas (sFas), caspase activity and caspase-generated neoepitope of the CK-18 proteolytic fragment (M30) were measured.ResultssFas was associated with fibrosis severity in pediatric (significant fibrosis p = 0.03, advanced fibrosis p = 0.01) and adult patients (advanced fibrosis p = 0.02). M30 levels were elevated in pediatric patients with severe steatosis (p = 0.01) while in adults no relation with any histological variable was observed. Caspase activity levels were higher in pediatric samples with significant fibrosis (p = 0.03) and they were associated with hepatitis severity (p = 0.04) in adult patients. The diagnostic accuracy evaluation demonstrated only a good performance for sFas to evaluate advanced fibrosis both in children (AUROC: 0.812) and adults (AUROC: 0.800) as well as for M30 to determine steatosis severity in children (AUROC: 0.833).ConclusionsSerum sFas could be considered a possible marker of advanced fibrosis both in pediatric and adult patient with CHC as well as M30 might be a good predictor of steatosis severity in children.

Noninvasive assessment of liver damage in chronic hepatitis B

To evaluate the efficacy of the aspartate aminotransferase/platelet ratio index (APRI) and neutrophil-lymphocyte (N/L) ratio to predict liver damage in chronic hepatitis B (CHB). We analyzed 89 patients diagnosed with CHB by percutaneous liver biopsy and 43 healthy subjects. Liver biopsy materials were stained with hematoxylin-eosin and Masson's trichrome. Patients' fibrosis scores and histological activity index (HAI) were calculated according to the Ishak scoring system. Fibrosis score was recognized as follows: F0-1 No /early-stage fibrosis, F2-6 significant fibrosis, F0-4 non-cirrhotic and F5-6 cirrhotic. Significant liver fibrosis was defined as an Ishak score of ≥ 2. APRI and N/L ratio calculation was made by blood test results. The hepatitis B and control group showed no difference in N/L ratios while there was a significant difference in terms of APRI scores (P < 0.001). Multiple logistic regression analysis revealed that the only independent predictive factor for liver fibrosis in CHB was platelet count. APRI score was significantly higher in cirrhotic patients than in non-cirrhotic patients. However, this significance was not confirmed by multiple logistic regression analysis. The optimum APRI score cut-off point to identify patients with cirrhosis was 1.01 with sensitivity, specificity, positive predictive value and negative predictive value of 62% (36%-86%), 74% (62%-83%), 29% (13%-49%) and 92% (82%-97%), respectively. In addition, correlation analyses revealed that N/L ratio has a negative and significant relationship with HAI (r = -0.218, P = 0.041). N/L ratio was negatively correlated with HAI. APRI score may be useful to exclude cirrhosis in CHB patients.

Mean platelet volume is increased in chronic hepatitis C patients with advanced fibrosis

Liver biopsy is the gold standard procedure for documenting liver damage in chronic hepatitis C (CHC), as for many other chronic liver diseases. Mean platelet volume (MPV) is a laboratory marker obtained from complete blood count (CBC) analysers in routine clinical practice. The goal of the present study was to evaluate whether MPV would be useful in predicting liver histologic severity in CHC. A total of 59 patients with CHC and 25 control subjects were recruited into the present study. There were 26 men and 33 women in the CHC group and 12 men and 13 women in the control group. MPV was recorded at the time of admission. The clinical characteristics of CHC patients, including demographics, laboratory and liver biopsy findings, were reviewed. A statistically significant increase in MPV values was observed in CHC patients (8.54 ± 0.63 fL) compared to healthy controls (7.65 ± 0.42 fL) (P < 0.001). Moreover, MPV values were significantly higher among patients with advanced fibrosis as compared to those with mild fibrosis (8.99 ± 0.57 fL vs. 8.19 ± 0.50 fL P < 0.001). Receiver operator characteristic (ROC) curve analysis suggested that the optimum cut-off point for MPV value in advanced fibrosis was 8.75 fL. (Sensitivity: 80.8%, specificity: 81.8%, positive predictive value [PPV] 77.8%, negative predictive value [NPV] 84.4%, accuracy 81.3%, AUC: 0.98 P < 0.001) The current study showed that MPV is increased in CHC with advanced fibrosis. Calculation of MPV along with the use of other markers may give further information about liver fibrosis severity in CHC.

Correlation between alanine aminotransferase level, HCV-RNA titer and fibrosis stage in chronic HCV genotype 4 infection

The relationship of serum alanine aminotransferase (ALT) level and viral replication to liver damage in chronic hepatitis C virus (HCV) patients remains unclear.The aim of the present study was to determine whether the stage of fibrosis correlates with HCV-RNA titer and/or serum ALT level in patients with chronic hepatitis C (genotype 4) infection.Clinical and biochemical characteristics were collected from 138 patients with chronic HCV genotype 4 infection. Quantitative HCV-RNA level measurement, HCV genotyping, and abdominal ultrasonography were investigated in all patients.Liver biopsy was done for 80 patients and the remaining 58 patients were examined using Fibroscan.Highly significant higher percentage of cases with high level of HCV viremia was found among patients with fibrosis stage 3 as compared to other stages of fibrosis. In contrast, grades of activity were independent of serum HCV-RNA titer.Patients with stages 1 and 4 hepatic fibrosis had significantly higher levels of ALT than patients with other stages of fibrosis. In contrast, an insignificant correlation was found between ALT level and grade of necroinflammation.In conclusion neither ALT level nor HCV viremia can reflect the histological liver change accurately. As a result, liver biopsy or other noninvasive procedures that measure liver stiffness (i.e., Fibroscan) remain essential for accurate staging of liver fibrosis in patients with genotype 4 chronic HCV infection.