Necroinflammatory Grade Research Articles

Serum microRNA-125b correlates with hepatitis B viral replication and liver necroinflammation

MicroRNAs (miRNAs) were recently reported to play an important role in hepatitis B virus (HBV) infection and related diseases. We evaluated the correlation between serum miRNA-125b, viral replication and liver necroinflammation in Chinese patients with chronic hepatitis B (CHB) infection. Serum miRNA-125b levels in samples from 211 CHB patients were determined by RT-PCR. Liver biopsies were collected from 138 patients. Serum miRNA-125b, miRNA-122 and miRNA-124 levels were determined. Correlations between serum miRNA-125b, viral replication and liver necroinflammation were analysed. The receiver operating characteristic (ROC) curve was used to assess the discriminating power of serum miRNA-125b to grade liver necroinflammation (G). HepG2.2.15 cells were transfected with miRNA-125b mimics. Intracellular viral core DNA was extracted and analysed by Southern blot. We found that serum miRNA-125b was positively correlated with the serum HBV DNA level. HBV replication capacity increased after transfection with miRNA-125b mimics. Patients with CHB with moderate-to-severe liver necroinflammation (G ≥2) showed significantly higher (p <0.001) serum miRNA-125b levels than those with G <2. In patients with alanine transaminase levels less than twice the upper limit of normal, serum miRNA-125b combined with miRNA-124 yielded an area under the ROC curve of 0.816, with 70.4% sensitivity and 84.9% specificity to discriminate the grade of liver necroinflammation (G ≥2). Hence, we concluded that miRNA-125b may enhance HBV replication. Serum miRNA-125b correlates with viral load. Serum miRNA-125b alone or combined with miRNA-124 has the potential to discriminate grades of liver necroinflammation, particularly in Chinese patients with CHB who have normal or mildly increased alanine transaminase levels.

The Histological Assessment of Hepatitis B Viral Activity in Patients with Heavy Alcohol Consumption

Objectives: Taiwan has a high prevalence of hepatitis B viral (HBV) infection with rising alcoholic liver disease. We investigated the histological assessment of viral hepatitis B activity in patients with concomitant HBV infection and alcoholism. Methods: 229 patients (33 with concomitant heavy alcoholism and HBV infection, 114 with HBV infection alone, and 82 with heavy alcoholism alone) were enrolled between 2009 and 2012 at Cathy General hospital and E-Da hospital. Results: Patients with concomitant alcoholism and HBV infection are male predominant and younger. 97.4% and 91.4% patients have detectable HBV DNA in patients with HBV infection without or with alcoholism, respectively. Patients with concomitant HBV infection and alcoholism have much piecemeal necrosis, confluent necrosis, focal necrosis, portal inflammation, necroinflammatory grading, and cirrhosis with Ishak stage 5-6 fibrosis. Moreover, patients with concomitant HBV infection and alcoholism also have much pericelluar fibrosis, sclerosing hyaline necrosis, non-alcoholic fatty liver disease (NAFLD) ballooning, NAFLD activity score (NAS) and NAFLD Stage 4 fibrosis (P<0.001). However, patients with alcoholism alone have much more steatosis than those with HBV infection with and without alcoholism. Conclusions: Patients having concomitant alcoholism and HBV infection develop the histological features of both alcoholic liver disease and viral hepatitis B. The assessment of hepatitis B viral activity in alcoholic liver disease depends on detectable viral load and histological features of viral hepatitis B in patients with concomitant HBV infection and alcoholism.

Liver fibrosis staging using T1 mapping on gadoxetic acid-enhanced MRI compared with DW imaging

To evaluate the utility of T1 mapping on gadoxetic acid-enhanced magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) for staging liver fibrosis. This retrospective study was approved by the institutional review board and included 145 patients (mean age: 54 years old; 115 men and 30 women). Necro-inflammatory activity grade (G) and liver fibrosis stage (S) were histopathologically determined. T1 relaxation time and apparent diffusion coefficient (ADC) of the liver were measured and the reduction rate of the T1 relaxation time (Δ%) was calculated. T1 relaxation time measurements were compared with ADC values according to S/G scores. Unenhanced hepatobiliary phase (HBP) and Δ% of T1 relaxation times showed significant correlations with S/G scores (rho: 0.28, 0.51, -0.35 for the S score, 0.26, 0.39, -0.26 for the G score, respectively, p<0.05). ADC values showed significant correlation with the S score (rho: -0.17, p = 0.04) and did not correlate significantly with the G score (rho: -0.07, p = 0.39). The areas under receiver operator characteristics (AUC) curve of unenhanced HBP, Δ% T1 relaxation time, and the ADC value were 0.68, 0.82, 0.71, 0.61 for the identification of S ≥ 3, and 0.63, 0.68, 0.62, 0.52 for the identification of G ≥ 3, respectively. The HBP T1 relaxation time was better than that of ADC for identification of S ≥ 3 (p = 0.0005) and G ≥ 3 (p = 0.014). The HBP T1 relaxation time measurement on gadoxetic acid-enhanced MRI images might be a potential biomarker in the staging of hepatic fibrosis, and was more accurate than the ADC measurement.

Efficacy of poly-unsaturated fatty acid therapy on patients with nonalcoholic steatohepatitis.

To examine whether poly-unsaturated fatty acid (PUFA) therapy is beneficial for improving nonalcoholic steatohepatitis (NASH). In total, 78 patients pathologically diagnosed with NASH were enrolled and were randomly assigned into the control group and the PUFA therapy group (added 50 mL PUFA with 1:1 ratio of EHA and DHA into daily diet). At the initial analysis and after 6 mo of PUFA therapy, parameters of interest including liver enzymes, lipid profiles, markers of inflammation and oxidation, and histological changes were evaluated and compared between these two groups. At the initial analysis, in patients with NASH, serum levels of alanine aminotransferase (ALT) and aspartase aminotransferase (AST) were slightly elevated. Triglyceride (TG), total cholesterol (TC) and low-density lipoprotein cholesterol levels, markers of systemic inflammation [C-reactive protein (CRP)] and oxidation [malondialdehyde (MDA)], as well as fibrosis parameters of type IV collagen and pro-collagen type III pro-peptide were also increased beyond the normal range. Six months later, ALT and AST levels were significantly reduced in the PUFA group compared with the control group. In addition, serum levels of TG and TC, CRP and MDA, and type IV collagen and pro-collagen type III pro-peptide were also simultaneously and significantly reduced. Of note, histological evaluation showed that steatosis grade, necro-inflammatory grade, fibrosis stage, and ballooning score were all profoundly improved in comparison to the control group, strongly suggesting that increased PUFA consumption was a potential way to offset NASH progression. Increased PUFA consumption is a potential promising approach for NASH prevention and reversal.

MR elastography of the liver at 3.0 T in diagnosing liver fibrosis grades; preliminary clinical experience.

To clarify the usefulness of 3.0-T MR elastography (MRE) in diagnosing the histological grades of liver fibrosis using preliminary clinical data. Between November 2012 and March 2014, MRE was applied to all patients who underwent liver MR study at a 3.0-T clinical unit. Among them, those who had pathological evaluation of liver tissue within 3 months from MR examinations were retrospectively recruited, and the liver stiffness measured by MRE was correlated with histological results. Institutional review board approved this study, waiving informed consent. There were 70 patients who met the inclusion criteria. Liver stiffness showed significant correlation with the pathological grades of liver fibrosis (rho = 0.89, p < 0.0001, Spearman's rank correlation). Areas under the receiver operating characteristic curve were 0.93, 0.95, 0.99 and 0.95 for fibrosis score greater than or equal to F1, F2, F3 and F4, with cut-off values of 3.13, 3.85, 4.28 and 5.38 kPa, respectively. Multivariate analysis suggested that grades of necroinflammation also affected liver stiffness, but to a significantly lesser degree as compared to fibrosis. 3.0-T clinical MRE was suggested to be sufficiently useful in assessing the grades of liver fibrosis. MR elastography may help clinicians assess patients with chronic liver diseases. Usefulness of 3.0-T MR elastography has rarely been reported. Measured liver stiffness correlated well with the histological grades of liver fibrosis. Measured liver stiffness was also affected by necroinflammation, but to a lesser degree. 3.0-T MRE could be a non-invasive alternative to liver biopsy.

Intrahepatic hepatitis B virus covalently closed circular DNA correlation with serum HBV DNA, serum HBsAg, alanine aminotransferase and age

To investigate the correlation between intrahepatic eovalently closed circular (ccc)DNA of hepatitis B virus (HBV) and pathogen-and patient-related parameters. Ultrasound-guided liver biopsies were obtained from 60 patients with chronic HBV infection. Levels of intrahepatic HBV cccDNA and serum HBV DNA were measured by quantitative fluorescence PCR. Level of serum hepatitis B surface antigen (HBsAg) was measured by chemiluminescence immunoassay. Clinical parameters, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (AKP), albumin, globulin (GLO), white blood cell, platelet, prothrombin-international normalized ratio, were measured by standard assay. Demographic information was recorded.The correlation between intrahepatic HBV cccDNA and pathogen-and patient-related parameters was assessed. Intrahepatic HBV cccDNA level was negatively correlated with age, GLO, ALT and grade of necroinflammation. Patients with age of 30 years or more showed significantly higher level of HBV cccDNA level than patients under 30 years-old (7.44±0.58 and 5.66±1.35; t=7.157, P less than 0.001). Intrahepatic HBV cccDNA level was positively correlated with serum HBV DNA level (r=0.916, P less than 0.001) and serum HBsAg level (r=0.727, P less than 0.001). The median ratio of HBV cccDNA to HBV DNA was 1.18, and of HBV cccDNA to HBsAg was 1.67. Intrahepatic HBV cccDNA levels decrease with age, level of ALT, level of GLO and grade of liver necroinflammation, but increase with level of serum HBV DNA and level of serum HBsAg. To a certain extent, serum HBV DNA and serum HBsAg levels may be a sufficient marker of intrahepatic HBV cccDNA levels.

Hepatitis C related chronic liver cirrhosis: feasibility of texture analysis of MR images for classification of fibrosis stage and necroinflammatory activity grade.

PurposeTo assess the feasibility of texture analysis for classifying fibrosis stage and necroinflammatory activity grade in patients with chronic hepatitis C on T2-weighted (T2W), T1-weighted (T1W) and Gd-EOB-DTPA-enhanced hepatocyte-phase (EOB-HP) imaging.Materials and methodsFrom April 2008 to June 2012, MR images from 123 patients with pathologically proven chronic hepatitis C were retrospectively analyzed. Texture parameters derived from histogram, gradient, run-length matrix, co-occurrence matrix, autoregressive model and wavelet transform methods were estimated with imaging software. Fisher, probability of classification error and average correlation, and mutual information coefficients were used to extract subsets of optimized texture features. Linear discriminant analysis in combination with 1-nearest neighbor classifier (LDA/1-NN) was used for lesion classification. In compliance with the software requirement, classification was performed based on datasets from all patients, the patient group with necroinflammatory activity grade 1, and that with fibrosis stage 4, respectively.ResultsBased on all patient dataset, LDA/1-NN produced misclassification rates of 28.46%, 35.77% and 20.33% for fibrosis staging and 34.15%, 25.20% and 28.46% for necroinflammatory activity grading in T2W, T1W and EOB-HP images. In the patient group with necroinflammatory activity grade 1, LDA/1-NN yielded misclassification rates of 5.00%, 0% and 12.50% for fibrosis staging in T2W, T1W and EOB-HP images respectively. In the patient group with fibrosis stage 4, LDA/1-NN yielded misclassification rates of 5.88%, 12.94% and 11.76% for necroinflammatory activity grading in T2W, T1W and EOB-HP images respectively.ConclusionTexture quantitative parameters of MR images facilitate classification of the fibrosis stage as well as necroinflammatory activity grade in chronic hepatitis C, especially after categorizing the input dataset according to the activity or fibrosis degree in order to remove the interference between the fibrosis stage and necroinflammatory activity grade on texture features.

Impact of Hepatic Steatosis on Response to Antiviral Therapy in Egyptian Patients with Chronic Hepatitis C

Background and study aim: Hepatic steatosis in hepatitis C virus (HCV) infected patients has been shown to enhance the progression of liver fibrosis and decrease the response to antiviral therapy. The current study is designed to investigate the impact of hepatic steatosis on the outcome of pegylated interferon and ribavirin combination therapy in patients with chronic hepatitis C genotype 4. Patients and Methods: A total number of 200 patients were selected from 270 patients who were referred to HCV Treatment Unit of New Mansoura General Hospital from February 2012 to August 2013 after taking an informed consent. They were 129 males and 71 females, their ages ranged from 25 to 55 years (mean value, 35.5±15.2). They had proven chronic hepatitis C virus based on history of exposure, clinical manifestations, positive anti-HCV antibody, positive HCV viremia, and liver biopsy findings suggestive of chronic hepatitis C. Results: Group I: included 100 patients (70 men and 30 women; mean age of 42.9±12 years) without liver steatosis. Group II: included 100 patients (59 men and 41 women; mean age of 45.23±11 years) with liver steatosis. In terms of steatosis grading using the NAS and METAVIR scoring systems, 50% had no staetosis while 8.5% had mild staetosis, 18.5% had moderate steatosis and 23% had severe steatosis. Body mass index of patients receiving interferon is significant between both groups. Hepatomegaly shows significant values between both groups. Platelets count, ALT, AST, S.Cholesterol & S.Triglycerides levels has statistically significant differences between group I (non steatotic) and group II (steatotic). There is statistically significant difference between both groups on necro-inflamatory activity grades. High statistical significance difference between grading of steatosis and Necro-inflammation. Statistical significance difference between grading of steatosis and fibrosis stages. Statistical significance difference between both groups at SVR and Steatosis has a negative effect on SVR by comparison to non steatotic group. High degree of hepatic steatosis has a negative impact on pagylated interferon and ribavirin therapy in chronic HCV genotype 4 minimizing sustained virologic response rates. Conclusion: Our study confirms that hepatic steatosis correlates with BMI, S.cholesterol, S.triglycerides, fibrosis, necro-inflammatory stages and has a negative impact on response to antiviral therapy.

Serum microRNA-29 levels correlate with disease progression in patients with chronic hepatitis B virus infection.

To investigate the role of serum microRNA-29 (miR-29) as a biomarker for the prediction of disease progression in patients with chronic hepatitis B virus (HBV) infection. Using real-time quantitative polymerase chain reaction assay, serum miR-29a, miR-29b and miR-29c levels were measured in patients with chronic HBV infection, and the correlation between serum miR-29 levels and the participants' liver biochemistry, fibrotic stage and necroinflammation grade were also evaluated. Altogether 91 patients with chronic HBV infection were divided by fibrotic stage into S0/1 (no or mild fibrosis), S2/3 (progressive fibrosis) and S4 (cirrhosis) subgroups, and 12 healthy individuals were also included in the study. Serum miR-29a and miR-29c in S0-3 were significantly higher than those in S4 patients (P < 0.001); however, the difference between S0/1 and S2/3 patients was not significant. miR-29b levels were higher in S0/1 patients than in other patient groups, but did not differ between S2/3 and S4 patients. At fibrotic stages of S0/1 and S2/3, patients with no or mild liver inflammation (G0/1) tended to express higher miR-29 levels than those with advanced inflammation (G2-4) (P > 0.05). miR-29a-c showed significant correlation with alanine transaminase levels (P < 0.05 for miR-29a, miR-29b and miR-29c) in S0-3 patients. The expression of miR-29 was highest in immune-tolerant patients (P < 0.001). Serum miR-29 levels are negatively correlated with liver fibrotic stages and necroinflammation grades in patients with chronic HBV infection. miR-29 appears to be a novel biomarkers for predicting disease progression in these patients.

HBsAg expression of liver correlates with histological activities and viral replication in chronic hepatitis B

Introduction. The intrahepatic hepatitis B surface antigens (HBsAg) expression is related to disease progression of chronic hepatitis B. We examined the features of intrahepatic HBsAg expression.Material and methods. A total of 181 patients with e antigen positive chronic hepatitis B were enrolled. Patterns and semi-quantitative measurement of intrahepatic HBsAg expression were analyzed. The association of intra-hepatic hepatitis HBsAg expression with clinical, viral, and histological characteristics was evaluated.Results. Higher necroinflammation grade and greater fibrosis stage accompanied with lower serum HBV DNA and HBsAg levels were observed in patients with type II ground glass hepatocytes and 2+/3+ scales of intrahepatic HBsAg expression. Basal core promoter T1762/A1764 mutations were strongly associated with the pattern of type II ground glass hepatocytes expression (P < 0.001) and higher level of HBsAg expression (9.3 ± 8.0% vs. 4.3 ± 5.0%, P = 0.008). In multivariate analysis, basal core promoter mutations (Odds ratio: 6.356, 95% confidence interval: 1.204 ~ 33.356, P = 0.029) was associated with 2+/3+ scale of HBsAg expression.Conclusion. Both pattern and levels of intrahepatic HBsAg expression were associated with severity of liver disease in e antigen positive chronic hepatitis B. Strong relationship between intrahepatic HBsAg expression and basal core promoter 1762/A1764 mutations indicated that HBsAg expression may be the histological manifestation of hepatitis B virus genomic evolution under host immune surveillance.

Noninvasive Measurement of Liver Fibrosis Using Transient Elastography in Pediatric Patients with Major Thalassemia Who Are Candidates for Hematopoietic Stem Cell Transplantation

Although liver biopsy is an invasive procedure, it remains the gold standard technique for the evaluation of hepatic fibrosis in different patients, including those with major thalassemia (MT). Recently, noninvasive imaging techniques, such as transient elastography, have emerged. We investigated the effectiveness of TE, in comparison to liver biopsy, for the evaluation of liver fibrosis in pediatric patients with MT who were candidates for hematopoietic stem cell transplantation (HSCT). Eighty-three pediatric MT patients (48 boys and 35 girls), who were candidates for HSCT, were included in this study. The median age was 8 years. Liver stiffness was assessed for all patients, before transplantation, using both TE, measured in kilopascals (kPa) and liver biopsy, based on the Metavir score. The diagnostic accuracy of TE and liver biopsy were estimated using linear discriminated analysis (the area under the receiver operating characteristic curves [AUROCs]). The median TE score was 4.3 kPa (range, 3.5 to 5.2). The TE value did not differ among patients with different ferritin levels (P = .53). TE increased proportionally to Metavir fibrosis stages (P < .001) and the necro-inflammatory grade (P < .001). The TE score also correlated to liver iron content (P < .001), liver size (P < .003), and Lucarelli risk classification (LRC) (P < .001). ROC curve analysis revealed moderate accuracy of the TE score for the diagnosis of fibrosis (AUROC = 73%) and for distinguishing individuals with a LRC III from those classified as I and II (AUROC = 82%). The TE score was also superior to Fibrosis-4 (AUROC = 61%) for the assessment of liver fibrosis and LRC differentiation. The results of this study demonstrated that TE can be a valuable method for assessing liver fibrosis and differentiating LRC III from the other 2 classes in pediatric patients with MT who have been selected for HSCT.

Interleukin-28B genetic variants in untreated Italian HCV-infected patients: a multicentre study.

Different prevalence of favourable IL28BCC genotype have been reported in studies performed in different countries around the world. Data on distribution of IL28B genotypes in healthy Italian subjects are lacking. Studies on prospectively collected untreated chronic HCV-infected Italian patients led to conflicting results. To investigate the prevalence of IL28B genotypes in untreated HCV-infected patients and in subjects able to clear HCV, and to compare them to the prevalence registered in healthy Italian controls. To evaluate IL28B prevalence across different HCV genotypes. IL28BCC was observed in 30.9% of chronic HCV patients, in 71.0% of subjects able to clear HCV infection and in 41.6% of the Italian controls. The frequency of IL28BCC was higher in HCV genotype 2 and 3 than in 1 (38.3 vs. 28.2) (P = 0.02). Levels of ALT higher in IL28BCC than in non-CC were observed regardless of HCV genotypes (P = 0.0014). IL28BCC frequencies progressively decline from subjects with spontaneous HCV clearance to normal non-infected subjects and to chronically infected. This study suggests that patients with IL28BCC, if genotype 1, are able to clear HCV more often than if genotype 2 and 3 infected, and that CC genotype is associated with higher grade of necro-inflammation.

Interleukin-28B rs12979860 C allele: Protective against advanced fibrosis in chronic hepatitis C genotype 1 infection.

Background and Aim: While genetic polymorphisms upstream of the interleukin-28B(IL28B) gene are associated with necroinflammatory activity grade in chronic hepatitis C virus genotype 1 (HCV-1) infection, any association with fibrosis is less definitive. Pretreatment liver biopsies in a cohort of treatment-naïve patients with HCV-1 were analyzed to evaluate associations between liver histology, and the rs12979860 and rs8099917 IL28B single nucleotide polymorphisms.Methods: Two hundred sixty-six patients with HCV-1 infection and pretreatment liver biopsy were tested for the rs12979860 and rs8099917 single nucleotide polymorphisms.Predictors of advanced fibrosis (METAVIR F3/4) and high activity grade (A2/3) were identified using multivariable logistic regression analysis.Results: Forty-four patients (16.5%) had advanced fibrosis and 141 patients (53.0%) high activity grade. Prevalence of rs12979860 IL28B genotype was: CC 45.7%, CT 42.7%, and TT 11.6%. Prevalence of advanced fibrosis was lower in those with IL28B CC genotype compared with those without (11.0% vs 21.3%; P = 0.03), with an increasing number of Talleles associated with a higher frequency of advanced fibrosis: CC 11.0%, CT 18.0%, TT33.3% (P = 0.01). Predictors of advanced fibrosis on multivariate analysis were platelet count (odds ratio [OR] 0.98, 95% confidence interval [CI] 0.97–0.99; P < 0.0001), high activity grade (OR 5.68, 95% CI% 1.86–17.32; P = 0.002), IL28B rs12979860 CC genotype(OR 0.36, 95% CI 0.14–0.93; P = 0.03), and aspartate aminotransferase (OR 1.02,95% CI 1.00–1.03; P = 0.046). No association was found between rs8099917 IL28B genotype and liver histology.Conclusions: IL28B rs12979860 CC genotype appears to be independently associated with a lower prevalence of advanced fibrosis stage in HCV-1 infection. This association warrants further evaluation.

Apparent diffusion coefficient value of hepatic fibrosis and inflammation in children with chronic hepatitis.

This study was done to prospectively evaluate the usefulness of apparent diffusion coefficient (ADC) in the diagnosis and grading of hepatic fibrosis and inflammation in children with chronic hepatitis. Institutional Review Board approval was obtained. This prospective study was carried out on 50 children with chronic hepatitis (mean age 8.3±3.2years; 33 boys and 17 girls) and 20 age- and sex-matched healthy control children. The children underwent diffusion-weighted magnetic resonance imaging of the liver. The ADC value of the liver was calculated. The hepatic fibrosis stages (F1-F6) and necroinflammatory activity grades (A1-A4) were calculated. The ADC values of different stages of hepatic fibrosis and grades of necroinflammatory activity were calculated. The mean ADC value of the liver parenchyma was 1.53±0.17×10(-3)mm(2)/s in children with chronic hepatitis and 1.74±0.16×10(-3)mm(2)/s in controls. The ADC value was significantly lower in children with hepatic fibrosis compared to controls (p=0.001). There was a significant difference (p=0.001) in ADC between mild (F1-F3) and advanced (F4-F6) stages of fibrosis. There was a significant difference (p=0.004) in ADC between mild (A1-A2) and advanced (A3-A4) grades of necroinflammation. The cut-off ADC values used to differentiate mild from advanced fibrosis and necroinflammation were 1.62 and 1.64mm(2)/s with an area under the curve of 0.898 and 0.807, respectively. The ADC value negatively correlated with stages of hepatic fibrosis (r=-0.799, p=0.001) and necroinflammatory activity grade (r=-0.468, p=0.001). We conclude that ADC value is an effective noninvasive parameter for the diagnosis and grading of hepatic fibrosis and inflammation in children with chronic hepatitis.

P785 PROJECTED HEALTH AND ECONOMIC IMPACT OF HEPATITIS C ON THE UNITED STATES VETERANS ADMINISTRATION HEALTH SYSTEM FROM 2014 TO 2024

Methods: Cases group (I) comprised 110 treatment naive CHC patients (78M, 32 F, mean age = 40.7±11.8 y) who underwent routine laboratory investigations. Decompensated cirrhosis was excluded. Assessment of plasma level of IL-18 (ELISA), detection of IL-18 gene polymorphisms at positions −607 C/A and −137 G/C by polymerase chain reaction sequence specific polymorphism (PCRSSP) analysis and Liver biopsy with METAVIR scoring were done. The control group (II) comprised 90 healthy subjects. Results: Serum levels of IL-18 were significantly higher in cases than the control group. A statistically highly significant (p < 0.001) positive correlation was found between IL-18 serum level both METAVIR necroinflammatory grade (A) and fibrosis stage (F). The A/A allele at −607 position was significantly more frequent (p< 0.05) in patients with F≤1. Conclusions: Higher IL-18 serum levels are found in CHC patients and positively correlate the severity of liver disease. The presence of A/A allele at −607 position of IL-18 gene promoter is associated with milder liver disease.

Diffusion weighted MRI in chronic viral hepatitis C: Correlation between apparent diffusion coefficient values and histopathological scores

Aim of the workTo assess the utility of hepatic ADC of diffusion weighted MRI in the diagnosis of liver fibrosis in chronic hepatitis C patients and to evaluate its relationship with both the stage of liver fibrosis and grade of necro-inflammation. Subjects and methodsForty patients with chronic viral hepatitis C and 30 healthy control group were examined by 1.5 T MRI scanner using DWI at b-values of 100, 400 and 800s/mm2. The mean ADC values of both patients and the control group were correlated to biopsy findings and graded according to METAVIR scoring system. ResultsThe mean ADC values of the liver at all b-values were statistically significantly lower in the study group than those of the control group. A strong negative correlation was found between the mean ADC value and the stage of fibrosis. No significant correlation was found between the mean ADC value and the grade of necroinflammation. ConclusionThe ADC value of diffusion weighted MRI can be used to distinguish between liver parenchyma of patients with chronic viral hepatitis C and healthy subjects and it is useful for estimation of the stage of liver fibrosis but not valuable in estimation of the grade of necro-inflammation.

Hepatic necro-inflammation and elevated liver enzymes: Evaluation with MRI perfusion imaging with gadoxetic acid in chronic hepatitis patients

To evaluate liver necro-inflammation and function by using gadoxetic acid-enhanced dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), with histological analysis as the reference standard. Seventy-nine subjects (21 healthy subjects; 58 chronic hepatitis patients) who received gadoxetic acid-enhanced DCE-MRI were divided into three subgroups: no (A0, n = 31), mild (A1, n = 27), and moderate-severe (A2-A3, n = 21) activities. Two DCE-MRI models were measured: (1) a dual-input single-compartment model to obtain absolute arterial, portal venous, and total blood flow, arterial fraction (ART), distribution volume, and mean transit time; (2) a curve analysis method to obtain peak, slope, and AUC (area under curve). The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels also obtained. Statistical testing included Kruskal-Wallis tests for continuous data, Pearson's correlation tests, and multiple linear regression analyses. Hepatic necro-inflammatory activity grades were significantly correlated with fibrotic stages, serum ALT level, ART and AUC. ART was helpful to predict the mild activity (≤ A1 versus >A1; Az = 0.728), whereas AUC could differentiate no activity from any activity (A0 versus >A0; Az = 0.703). Peak, slope and AUC were all associated with AST and ALT (p < 0.05). Gadoxetic acid-enhanced DCE-MRI parameters may be used to evaluate the severity of hepatic necro-inflammation and function.

Comparison of hepatitis B surface antigen and e antigen in predicting liver histology in hepatitis B e antigen-positive chronic hepatitis B patients.

The purpose of this study was to determine the relationship between hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) levels and liver histology in HBeAg-positive patients with chronic hepatitis B virus (CHB) infection. Serum HBsAg and HBeAg levels were analyzed, and liver biopsies were obtained from 203 HBeAg-positive CHB patients (62.6% males; median age 31.3years). The upper limit of normal (ULN) for ALT in this study was 30 and 19U/L for males and females, respectively. Histologic assessment was based on Scheuer classification. ALT <2 × ULN, fibrosis stage <S2, and necro-inflammation grade <G2 were noted in 70 (34.5%), 141 (69.5%), and 105 (51.7%) patients, respectively. Patients with significant histology (fibrosis stage ≥S2 and/or fibrosis stage of 1 plus inflammation grade ≥2) had significantly lower median HBsAg (13,998.4 and 42,186.5IU/mL, respectively, p<0.001) and HBeAg levels (540.5 and 1,206.8S/CO, respectively, p<0.001) than patients with insignificant histology. Among patients with ALT <2 × ULN, the area under the ROC curve for serum HBsAg and HBeAg levels was 0.76 and 0.70, respectively. Using a cutoff value of 17,558IU/mL for HBsAg and 875.6S/CO for HBeAg in patients with ALT <2×ULN, positive predictive values for insignificant histology were 87 and 86.8%, respectively, whereas the negative predictive values were 50 and 47.1%, respectively. Among HBeAg-positive patients with ALT <2 × ULN, high-serum HBsAg and HBeAg levels can equally accurately predict insignificant histology.

The impact of clinicopathological parameters in predicting response to pegylated interferon and ribavirin in chronic hepatitis C patients

ObjectivesThis study aimed to investigate the impact of clinical and histopathological changes in liver tissue of responders and nonresponders to standard pegylated interferon (Peg-IFN) and ribavirin (RBV) therapy and to determine whether they could predict treatment outcome or not.BackgroundHepatitis C virus (HCV) infection is a major health problem worldwide. Combination therapy of Peg-IFN and RBV has been recognized as a standard treatment for HCV infection. Unfortunately, this standard therapy produces a sustained virological response in only 50% of HCV-infected patients. Clinical and histological findings may play a role in predicting response to standard Peg-IFN/RBV therapy.Patients and methodsThis retrospective study included 64 patients with chronic HCV who were treated with Peg-IFNa/RBV. According to their response to treatment, they were classified into responders (n = 34) and nonresponders (n = 30). Pretreatment liver biopsies were evaluated histopathologically for necroinflammatory grade and fibrosis stage according to the modified Ishak and Metavir scoring systems for chronic hepatitis. Other pathological findings were also reported. Demographic, laboratory, and histopathological results were subjected to a statistical analysis.ResultsThe current study showed that the age of the patients (P = 0.003), sex (P = 0.027), and serum a-fetoprotein level (P = 0.046) were the parameters that showed a statistically significant difference between responders and nonresponders to interferon therapy. However, the grade of necroinflammation, stage of fibrosis as well as other pathological changes did not show a statistically significant difference between both groups.ConclusionThe current study showed that young age, female sex, and the baseline serum level of a-fetoprotein are the parameters that favored response to interferon and RBV therapy in chronic HCV Egyptian patients, whereas histopathological changes played no role in predicting response to treatment.

Elevated miR-33a and miR-224 in steatotic chronic hepatitis C liver biopsies.

To assess the expression of selected microRNAs (miRNA) in hepatitis C, steatotic hepatitis C, noninfected steatotic and normal liver tissues. The relative expression levels of miR-21, miR-33a, miR-96, miR-122, miR-125b, miR-221 and miR-224 were determined in 76 RNA samples isolated from 18 non-steatotic and 28 steatotic chronic hepatitis C (CHC and CHC-Steatosis, respectively) cases, 18 non-infected, steatotic liver biopsies of metabolic origin (Steatosis) and 12 normal formalin-fixed paraffin-embedded liver tissues using TaqMan MicroRNA Assays. All CHC biopsy samples were obtained prior to initiating therapy. Patients' serum biochemical values, which included glucose, triglyceride, cholesterol, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl-transferase (GGT), alkaline phosphatase (AP), were obtained and correlated with relative miRNA expression. When compared with control non-infected liver samples, miR-122 and miR-221 levels were reduced in CHC-Steatosis (P < 0.03) and in CHC, CHC-Steatosis and Steatosis (P < 0.01). Alternatively, the expression of miR-33a and miR-224 were elevated in CHC-Steatosis and Steatosis in comparison to control tissue (P < 0.01). The levels of miR-33a and miR-224 in CHC-Steatosis (P < 0.02) and miR-224 in Steatosis (P < 0.001) were increased in comparison to CHC samples. By contrast, the expression of miR-21 did not differ statistically between diseased and normal liver samples. Levels of miR-33a correlated negatively with serum AST and AP levels in Steatosis as well as with necroinflammatory grade in CHC, whereas miR-21 correlated positively with AST in Steatosis and displayed negative correlation with triglyceride level in CHC-Steatosis. In contrast, miRNA levels were not correlated with ALT, GGT, cholesterol levels or fibrosis stage. Differences in miRNA expression were observed between CHC and steatotic CHC, CHC and steatotic liver, but not between steatotic CHC and steatotic liver of metabolic origin.