Chronic Hepatitis Patients Research Articles

Algunas consideraciones sobre clonorquiasis sinensis y un método simple para su diagnóstico

Three cases are reported of chinese residents in Nicaragua showing nervous disorders; two of then had been diagnosed in American clinics as chronic hepatitis patients. Their Cantonese origin and the symtomatology suggested the possibility of clonorchiasi, sinensis. Stool tests had been negative for Clonorchis. A simple procedure was then tried out which gave good results: that of injecting a lipotropic complex and examining the feces 48 hours later. In such circumstances all three patients showed abundant Clonorchis eggs.

Intrahepatic CD206+ macrophages contribute to inflammation in advanced viral-related liver disease

Liver inflammation is key in the progression of chronic viral hepatitis to cirrhosis and hepatocellular carcinoma. The magnitude of viral replication and the specific anti-viral immune responses should govern the degree of inflammation, but a direct correlation is not consistently found in chronic viral hepatitis patients. We aim to better define the mechanisms that contribute to chronic liver inflammation. Intrahepatic CD14+ myeloid cells from healthy donors (n=19) and patients with viral-related liver cirrhosis (HBV, HBV/HDV or HCV; n=15) were subjected to detailed phenotypic, molecular and functional characterisation. Unsupervised analysis of multi-parametric data showed that liver disease was associated with the intrahepatic expansion of activated myeloid cells mainly composed of pro-inflammatory CD14+HLA-DRhiCD206+ cells, which spontaneously produced TNFα and GM-CSF. These cells only showed heightened pro-inflammatory responses to bacterial TLR agonists and were more refractory to endotoxin-induced tolerance. A liver-specific enrichment of CD14+HLA-DRhiCD206+ cells was also detected in a humanised mouse model of liver inflammation. This accumulation was abrogated following oral antibiotic treatment, suggesting a direct involvement of translocated gut-derived microbial products in liver injury. Viral-related chronic liver inflammation is driven by the interplay between non-endotoxin-tolerant pro-inflammatory CD14+HLA-DRhiCD206+ myeloid cells and translocated bacterial products. Deciphering this mechanism paves the way for the development of therapeutic strategies specifically targeting CD206+ myeloid cells in viral-related liver disease patients. Lay summary: Viral-related chronic liver disease is driven by intrahepatic pro-inflammatory myeloid cells accumulating in a gut-derived bacterial product-dependent manner. Our findings support the use of oral antibiotics to ameliorate liver inflammation in these patients.

Hepatitis B Virus Immunopathology, Model Systems, and Current Therapies.

Most people develop acute hepatitis B virus (HBV)-related hepatitis that is controlled by both humoral and cellular immune responses following acute infection. However, a number of individuals in HBV-endemic areas fail to resolve the infection and consequently become chronic carriers. While a vaccine is available and new antiviral drugs are being developed, elimination of persistently infected cells is still a major issue. Standard treatment in HBV infection includes IFN-α, nucleoside, or nucleotide analogs, which has direct antiviral activity and immune modulatory capacities. However, immunological control of the virus is often not durable. A robust T-cell response is associated with control of HBV infection and liver damage; however, HBV-specific T cells are deleted, dysfunctional, or become exhausted in chronic hepatitis patients. As a result, efforts to restore virus-specific T-cell immunity in chronic HBV patients using antiviral therapy, immunomodulatory cytokines, or therapeutic vaccination have had little success. Adoptive cell transfer of T cells with specificity for HBV antigen+ cells represents an approach aiming to ultimately eliminate residual hepatocytes carrying HBV covalently closed circular DNA (cccDNA). Here, we discuss recent findings describing HBV immunopathology, model systems, and current therapies.

Screening differential circular RNA expression profiles reveals hsa_circ_0004018 is associated with hepatocellular carcinoma.

Circular RNAs (circRNAs) have been emerged as an indispensable part of endogenous RNA network. However, the expression significance of circRNAs in hepatocellular carcinoma (HCC) is rarely revealed. The aim of this study was to determine the circRNA expression profile in HCC, and to investigate their clinical significances and relevant mechanisms for cancer progression. The global circRNA expression profile in HCC was measured by circRNA microarray. Levels of one representative circRNAs, hsa_circ_0004018, were confirmed by real-time reverse transcription-polymerase chain reaction. The expression levels of hsa_circ_0004018 in HCC were significantly lower compared with para-tumorous tissue (P<0.001). Our data further showed that lower expression of hsa_circ_0004018 was correlated with serum alpha-fetoprotein (AFP) level, tumor diameters, differentiation, Barcelona Clinic Liver Cancer stage and Tumor-node-metastasis stage. More importantly, we detected liver tissues from chronic hepatitis, cirrhosis and HCC patients; and found that hsa_circ_0004018 harbored HCC-stage-specific expression features in diverse chronic liver diseases (P<0.001). The area under receiver operating characteristic curve was up to 0.848 (95% CI=0.803–0.894, P<0.001). The sensitivity and specificity were 0.716 and 0.815, respectively. Finally, hsa_circ_0004018 might be involved in cancer-related pathways via interactions with miRNAs.

Angiopoietin-like protein 3 and 4 expression 4 and their serum levels in hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC) is the 6th most common cancer and the 3rd leading cause of cancer causing death allover the world. The aim of this research to explore the clinical relevance of blood angiopoietin-like protein-3 (ANGPTL3) and ANGPTL4 expression and their proteins levels as non invasive biomarkers in cirrhotic and HCC patients and their influence on the clinicopathological features of HCC. Material and methodsThis work comprised 200 patients with chronic hepatitis (120 cases complicated with cirrhosis, 80 patients with primary HCC) and 100 controls. circulating ANGPTL3 and ANGPTL4 expression was estimated by real-time polymerase chain reaction (RT-PCR). ANGPTL3 and ANGPTL4 protein levels were determined by enzyme-linked immunosorbent assay (ELISA). ResultsThe circulating ANGPTL3 and ANGPTL 4 expression was significantly elevated in HCC cases compared to chronic hepatitis patients and controls. There were much more serum ANGPTL3 and ANGPTL4 values in HCC and chronic hepatitis patients as compared to controls, but we couldn't detect this significance between chronic hepatitis and HCC cases as regards ANGPTL4. By Multiple stepwise linear regression analysis, an increased ANGPTL3 expression, alpha-fetoprotein (AFP), serum ANGPTL 3 levels, Child–Pugh grade were significantly assosciatedassociated with increased risk of HCC. Logistic regression analysis revealed that ANGPTL 3 expression and AFP levels were the only pridectorspredictors of HCC (odd's ratio (OR)=8.9; 8.6 respectively, P=0.003). Receiver operator characteristic (ROC) demonsterated that serum ANGPTL3 and ANGPTL4 levels were usufuluseful biomarkers discriminating chronic hepatitis cases from controls (AUC=0.820,0.887, respectively P<0.001). However, they fail to discriminate HCC patients from chronic hepatitis patients (P=0.27,0.12 respectively). Moreover, ANGPTL3 and ANGPTL 4 expression were promising biomarkers discriminating chronic hepatitis cases from controls and those HCC cases from chronic hepatitis patients (P<0.001). Combined ANGPTL3 expression and serum level wasn't useful in discriminating HCC patient from chronic hepatitis (P=0.09). In contrast, combined ANGPTL4 expression and serum level was an useful biomarker discriminating HCC cases from chronic hepatitis. ConclusionANGPTL3 and ANGPTL 4 expression and serum levels can be promising non invasive biomarkers in diagnosis of chronic hepatitis and HCC especially their expression could be useful in discriminating HCC from chronic hepatitis patients.

Effect of indigenous interferon - alpha on Hepatitis B virus deoxyribonucleic acid level in hepatitis b e antigen-positive chronic Hepatitis B patients

&lt;p class="ABS"&gt;&lt;span class="ABS_Bold-Italic" lang="en-GB"&gt;Background and Objective:&lt;/span&gt; HBeAg-positive chronic hepatitis B patients have high serum HBV DNA level showing high viral replication. Goal of treatment of hepatitis B is to prevent cirrhosis, hepatic failure and hepatocellular carcinoma by serum alanine transaminase (ALT) normalization, decrease in serum hepatitis B virus (HBV) deoxyribonucleic acid (DNA) and loss in hepatitis B e antigen (HBeAg). Interferons (IFNs) have antiviral, anti-proliferative, and immunomodulatory effects. IFN-&lt;span class="Symbol_Bold"&gt;α&lt;/span&gt; is effective in suppressing HBV replication and in inducing remission of liver disease. &lt;span class="ABS_Bold-Italic" lang="en-GB"&gt;Materials and Methods:&lt;/span&gt; In this prospective, single treatment arm study, HBeAg-positive chronic hepatitis patients without decompensated liver disease were enrolled to receive indigenous recombinant IFN-&lt;span class="Symbol_Bold"&gt;α&lt;/span&gt; 2b in the dose of 5 MU daily for 6 days a week subcutaneously for 16 weeks. Quantitative HBV-DNA, HBeAg, and hepatitis B surface antigen (HBsAg) were assessed at baseline and at the end of treatment. ALT level assessment was done at baseline and during therapy at week 1, week 2, week 8, week 12, and week 16. &lt;span class="ABS_Bold-Italic" lang="en-GB"&gt;Res&lt;/span&gt;&lt;span class="ABS_Bold-Italic" lang="en-GB"&gt;ults:&lt;/span&gt; Out of 37 patients enrolled in the study, 8 patients (21.62%) did not complete study due to lost to follow-up (3 patients), discontinuation due to adverse event (3 patients), and consent withdrawal (2 patients). Among 29 patients who completed the study, 10 patients (34.48%) had clearance of HBeAg and 1 patient (3.44%) had lost HBsAg after 16 weeks of therapy. Mean ALT level started decreasing after 4 weeks of therapy but did not come to normal range till 16 weeks of therapy. At least 2 log decreases in HBV DNA was observed in 9 (31.03%) patients and at least 1 log decrease in 18 (62.06%) patients. Overall decline in HBV DNA level was observed in 62% patients after 16 weeks of therapy. &lt;span class="ABS_Bold-Italic" lang="en-GB"&gt;Conclusion:&lt;/span&gt; IFN-&lt;span class="Symbol_Bold"&gt;α&lt;/span&gt; treatment does result in HBeAg and HBsAg loss and decreases HBV-DNA levels in chronic hepatitis B patients. Most of adverse events were mild to moderate in intensity. So, interferon-&lt;span class="Symbol_Bold"&gt;α&lt;/span&gt; therapy was well tolerated, safe, and efficacious to treat HBeAg-positive chronic hepatitis B patients without decompensated liver disease.&lt;/p&gt;

The use of Chinese herbal medicine as an adjuvant therapy to reduce incidence of chronic hepatitis in colon cancer patients: A Taiwanese population-based cohort study

Ethnopharmacological relevanceThere is a decided lack of in-depth studies to evaluate the effectiveness of Chinese Herbal Medicine (CHM) as an adjuvant therapy on the incidence of chronic hepatitis in patients with colon cancer. Aim of the studyThe aim of this study is to assess whether CHM treatment decreased the incidence of chronic hepatitis in colon cancer patients who received conventional Western medical treatment. Materials and methodsA Taiwanese nationwide population-based study of colon cancer patients receiving Western medicine treatment in conjunction with CHM treatment, using data provided by the National Health Insurance (NHI) Research Database, was conducted. A total of 61676 patients were diagnosed with colon cancer in Taiwan within the defined study period, from 1997 to 2010. After randomly equal matching for age, sex, excluding patients younger than 18 years of age, chronic hepatitis before colon cancer diagnosis date, receiving acupuncture and/or moxibustion and taking CHM for less than 30 days, data from 155 patients were analyzed. Hazard ratios of incidence rate of chronic hepatitis were used to determine the influence of CHM and the therapeutic potential of herbal products in treating patients with colon cancer. ResultsCHM used for patients with colon cancer exhibited significantly decreased incidence rates of chronic hepatitis [hazard ratio (HR)=0.53; 95% confidence interval (CI):0.38–0.74], with multivariate adjustment, compared to those without CHM use. The protective effect of CHM treatment with statistical significance across the stratification of age, gender, co-morbidity and treatment modality was noted. The cumulative incidence of chronic hepatitis was also reduced in patients with colon cancer receiving CHM treatment during a five-year period. In this study, we provide the ten most used single herbs and herbal formulas that were prescribed for patients with colon cancer; moreover, we identify the eight single herbs and five formulas used in CHM treatment which significantly decreased incidence of chronic hepatitis among colon cancer patients. ConclusionsThis nationwide retrospective cohort study determined that therapy using CHM as an adjuvant modality may have a significant impact on liver protection in patients with colon cancer.

Real-world efficacy and safety of daclatasvir and asunaprevir therapy for hepatitis C virus-infected cirrhosis patients.

Daclatasvir and asunaprevir combination therapy has shown a high virological response for chronic genotype 1 hepatitis C virus (HCV) infected-patients. However, the real-world efficacy and safety of the therapy for patients with cirrhosis are unknown. A total of 252 patients with genotype 1 HCV infection (158 with chronic hepatitis and 94 with compensated liver cirrhosis) were treated with 24 weeks of daclatasvir and asunaprevir combination therapy. Plasma concentrations of daclatasvir and asunaprevir at day 5 of treatment, end-of-treatment response, sustained virological response (SVR), and the frequencies of adverse events were analyzed. Plasma asunaprevir concentration was significantly higher, and daclatasvir concentration tended to be higher, in cirrhosis patients compared with chronic hepatitis patients. End-of-treatment response was achieved in 95.6% and 94.7% of chronic hepatitis and cirrhosis patients, respectively, and SVR was achieved in 94.3% and 92.6%. Although pre-treatment NS5A drug resistant-associated variants were detected, a high SVR rate was achieved when the population frequency of the variant was low. The frequencies of treatment-related adverse events in cirrhosis patients were similar to those in chronic hepatitis patients. Treatment discontinuation due to adverse events occurred in three and two patients in chronic hepatitis and cirrhosis groups, respectively; however, four out of five patients with treatment discontinuation nonetheless achieved SVR. Patients with compensated liver cirrhosis have similar virological response and tolerance for daclatasvir plus asunaprevir therapy to patients with chronic hepatitis. This combination therapy might offer a safe and effective treatment for chronic HCV infected-patients with compensated cirrhosis.

Efficacy and safety of sofosbuvir-based regimens in chronic hepatitis C patients on dialysis.

Patients with end-stage renal disease (ESRD) have poor treatment tolerance and outcome to interferon-based regimens. Sofosbuvir-based regimens have improved treatment success in chronic hepatitis C. There is limited data in ESRD patients as sofosbuvir is excreted by the kidney. Several small studies have shown good results. Sixteen consecutive patients of ESRD (on dialysis) and chronic hepatitis C were treated with sofosbuvir-based regimens as they were prospective kidney transplantation recipients, at a tertiary care center in north India. Sofosbuvir was given 400mg on alternate days. Data is shown as number, mean (SD), and median (range). Sixteen patients (12 males) aged 45±12 years received sofosbuvir-based treatment. These patients were on hemodialysis from 10 (2-48) months. Eleven of these patients had genotype 1, four had genotype 3, and one had genotype 4 infection; baseline RNA was 7 (5-8) log. The following treatment regimens were used: sofosbuvir, ribavirin, and low dose peginterferon (n=8; 6 genotype 1 and one each had genotype 3 and 4); sofosbuvir and daclatasvir (n=7); sofosbuvir, ribavirin, and daclatasvir (n=1). Ten patients achieved end of treatment response and 8 (80%) of these achieved sustained virological response at 12weeks (SVR12); six are on treatment. Two patients with genotype one (including one with cirrhosis) had relapse. Seven patients needed blood transfusion; interferon was stopped in one due to thrombocytopenia. Fatigue was present in 4 patients. Sofosbuvir-based regimens can be used in ESRD patients on dialysis with good efficacy.

Assessment of Educational Needs and Quality of Life of Chronic Hepatitis Patients

BackgroundPatient education is crucial in improving the health-related quality of life (HRQOL) of patients. At the same, understanding the concerns and needs of patients is essential in providing appropriate education. This study assessed the educational needs and HRQOL experienced by chronic hepatitis patients.MethodsWe developed structured questionnaires with satisfactory validity and reliability to assess the educational needs of patients. HROQL was measured using a generic Short Form 36 (SF-36) and a liver disease-specific Chronic Liver Disease Questionnaire (CLDQ). Descriptive statistic measures and Pearson’s correlation analysis were applied for data analysis.ResultsA total of 135 subjects were recruited from two regional teaching hospitals in Taiwan. “Disease characteristics and management” exhibited the highest mean score (3.17) among all the subscales of educational needs. In comparison with those without antiviral therapy, chronic hepatitis patients undergoing antiviral treatment scored significantly higher on all subscales of educational needs, especially on “side effects of antiviral treatment” (p < 0.010). The median range of the physical component summary score was 45.94, the mental component summary score was 49.37, and the mean CLDQ was 5.70. Several domains of educational needs were significantly inversely correlated with the CLDQ and SF-36 subscales.ConclusionsEducation is highly required by chronic hepatitis patients, especially those receiving antiviral therapy and patients with poor HRQOL. These findings can serve as a useful reference for nursing personnel who perform needs assessment to develop individual nursing instruction and thereby improve the quality of care for chronic hepatitis patients.

Circulating CD14+ HLA-DR-/low myeloid-derived suppressor cells predicted early recurrence of hepatocellular carcinoma after surgery.

Myeloid-derived suppressor cells (MDSCs) play an important role in tumor progression. The aim of the present study was to investigate the prognostic value of MDSCs for early recurrence of hepatocellular carcinoma (HCC) in patients undergoing curative resection. Myeloid-derived suppressor cells were measured by flow cytometry. The correlation between MDSCs and tumor recurrence was analyzed using a cohort of 183 patients who underwent curative resection between February 2014 and July 2015. Prognostic significance was further assessed using Kaplan-Meier survival estimates and log-rank tests. In vivo, CD14+ HLA-DR-/low MDSCs inhibit T cell proliferation and secretion. The frequency of CD14+ HLA-DR-/low MDSCs was significantly higher in HCC patients (3.7 ± 5.3%, n = 183) than in chronic hepatitis patients (1.4 ± 0.6%, n = 25) and healthy controls (1.1 ± 0.5%, n = 50). High frequency of MDSCs was significantly correlated with recurrence (time to recurrence) (P <0.001) and overall survival (P = 0.034). Patients with HCC in the high MDSC group were prone to more vascular invasion (P = 0.018) and high systemic immune-inflammation index (SII) (P = 0.009) than those in the low MDSC group. Scatter-plot analyses revealed a significant positive correlation between the SII level and the frequency of MDSCs (r = 0.188, P = 0.011). Patients with HCC with a high MDSC frequency and high SII level had significantly shorter time to recurrence (P <0.001) and overall survival (P = 0.028) than those with a low MDSC frequency and low SII. An increased frequency of MDSCs was correlated with early recurrence and predicted the prognosis of patients with HCC undergoing curative resection. The HCC patients with high frequency of MDSCs should be provided more advanced management and frequent monitoring.

Study of disease burden of chronic hepatitis B and C patients in Shanghai based on Bronfenbrenner' s ecological systems theory: a community-based survey

Objective: To systemically analyze family burden, quality of life of chronic hepatitis B and C patients in Shanghai and related influencing factors. Methods: A representative sample of chronic hepatitis patients (n=1 478) and their family members (n=1 478) was randomly selected through a multi-stage cluster sampling from 30 communities in 10 districts of Shanghai. One patient and one family member of each family were interviewed using different questionnaires to collect related information. Based on Bronfenbrenner' s ecological systems, psychological measurement, two-level random intercept model and multivariable structural equation model were applied to determine the effects and directions of the factors between life quality of chronic hepatitis patients and family burden. Results: The mean score of quality of life of chronic hepatitis patients in Shanghai was 78.70 ± 13.25, the score of " specific module" was highest and the score of " social function" was lowest. Additionally, the mean score of burden reported by the family members was 12.62±10.74, the score of " financial burden" was highest, and the score of " effect on family member' s health" was lowest. Multivariable structural equation model indicated that eight factors were related with life quality and family burden of patients with chronic hepatitis. Among them, HCV infection, elevated serum alanine aminotransferase level, average monthly cost for patient >3 000 yuan (RMB) and poor health of family members were the direct risk factors for the life quality of the patients as well as family burden. The factor of drinking more than once a week influenced the patients' life quality directly and family burden indirectly. On the contrary, the factors of local household registration, hospitalization and family member's indifferent attitude to hepatitis B vaccination influenced the family burden of the chronic hepatitis patients directly and the life quality of the patients indirectly. Conclusion: The findings could be used in the development of community based management and intervention of chronic hepatitis patients in Shanghai.

Chinese Herbal Medicine as an Adjunctive Therapy Ameliorated the Incidence of Chronic Hepatitis in Patients with Breast Cancer: A Nationwide Population-Based Cohort Study.

We conducted a National Health Insurance Research Database-based Taiwanese nationwide population-based cohort study to evaluate whether Chinese herbal medicine (CHM) treatment decreased the incidence of chronic hepatitis in breast cancer patients receiving chemotherapy and/or radiotherapy. A total of 81171 patients were diagnosed with breast cancer within the defined study period. After randomly equal matching, data from 13856 patients were analyzed. Hazard ratios of incidence rate of chronic hepatitis were used to determine the influence and therapeutic potential of CHM in patients with breast cancer. The patients with breast cancer receiving CHM treatment exhibited a significantly decreased incidence rate of chronic hepatitis even across the stratification of age, CCI score, and treatments. The cumulative incidence of chronic hepatitis for a period of seven years after initial breast cancer diagnosis was also reduced in the patients receiving CHM treatment. The ten most commonly used single herbs and formulas were effective in protecting liver function in patients with breast cancer, where Hedyotis diffusa and Jia-Wei-Xiao-Yao-San were the most commonly used herbal agents. In conclusion, our study provided information that western medicine therapy combined with CHM as an adjuvant modality may have a significant impact on liver protection in patients with breast cancer.

Naturally occurring mutations in the reverse transcriptase region of hepatitis B virus polymerase from treatment-naïve Korean patients infected with genotype C2

AIMTo report naturally occurring mutations in the reverse transcriptase region (RT) of hepatitis B virus (HBV) polymerase from treatment naïve Korean chronic patients infected with genotype C2.METHODSHere, full-length HBV reverse transcriptase RT sequences were amplified and sequenced from 131 treatment naïve Korean patients chronically infected with hepatitis B genotype C2. The patients had two distinct clinical statuses: 59 patients with chronic hepatitis (CH) and 72 patients with hepatocellular carcinoma (HCC). The deduced amino acids (AAs) at 42 previously reported potential nucleos(t)ide analog resistance (NAr) mutation positions in the RT region were analyzed.RESULTSPotential NAr mutations involving 24 positions were found in 79 of the 131 patients (60.3%). Notably, AA substitutions at 2 positions (rt184 and rt204) involved in primary drug resistance and at 2 positions (rt80 and rt180) that functioned as secondary/compensatory mutations were detected in 10 patients (1 CH patient and 9 HCC patients) and 7 patients (1 CH and 6 HCC patients), respectively. The overall mutation frequencies in the HCC patients (3.17%, 96/3024 mutations) were significantly higher than the frequencies in the CH patients (2.09%, 52/2478 mutations) (P = 0.003). In addition, a total of 3 NAr positions, rt80, rt139 and rt204 were found to be significantly related to HCC from treatment naïve Korean patients.CONCLUSIONOur data showed that naturally occurring NAr mutations in South Korea might contribute to liver disease progression (particularly HCC generation) in chronic patients with genotype C2 infections.

Circulating LncRNAs Serve as Diagnostic Markers for Hepatocellular Carcinoma

Background/Aims: Circulating (serous or plasmic) long non-coding RNA (lncRNA) as biomarkers for predicting the diagnosis or prognosis of human disease have been well documented. Due to the sensibility or specificity limitation of Alpha Fetoprotein (AFP), a cluster lncRNAs were revealed as fingerprints for hepatocellular carcinoma (HCC). In this study, we enrolled all the reported circulating lncRNAs in HCC as candidate targets and examined in an independent cohort. Methods: The candidate lncRNAs were determined by qRT-PCR divided into training and validation sets. The risk score analysis was employed to evaluate the potential diagnosis ability of the lncRNAs independently or combining with AFP value. The receiver operating characteristic curve (ROC) was applied for presentation of sensibility or specificity. Results: Among the ten candidate circulating lncRNA, LINC00152, RP11-160H22.5, XLOC014172 and LOC149086 were screened with significant difference in training set. Further investigation in validation set indicated LINC00152, RP11-160H22.5 and XLOC014172 might be the fingerprints for HCC comparing with chronic hepatitis (CH) patients or healthy controls. The risk score analysis revealed the combination of three lncRNAs with AFP could distinguish the HCC from either CH or healthy control with the area under curve value (AUC) of 0.986 and 0.985, respectively. Conclusion: The three lncRNAs may act as novel biomarkers for acting as fingerprint in HCC combining with AFP.

THU-497 - Diagnostic accuracy of magnetic resonance elastography with liver fibrosis assessment in chronic viral hepatitis patients

THU-497 - Diagnostic accuracy of magnetic resonance elastography with liver fibrosis assessment in chronic viral hepatitis patients

Haemostatic Profile of Patients with Chronic Liver Disease- its Correlation with Severity and Outcome.

The liver plays an important role in the haemostatic system as it synthesizes the majority of coagulation factors and fibrinolytic proteins. The present study was planned to determine the range of haemostatic defects in patients of chronic liver diseases. Test performed included Prothrombin Time (PT), activated Partial Thromboplastin Time (aPTT), Thrombin Time (TT), Fibrinogen, Protein C, D Dimer and platelet count. Comparisons between groups frequencies and groups means were made using Chi-square test and Student's t-test, respectively. In cirrhosis group PT, aPTT, TT and D Dimer level were significantly increased compared to Chronic Hepatitis (CH) and control group (p<0.001 for all comparisons). Serum fibrinogen, Protein C and platelet count were significantly reduced in cirrhosis patients compared to CH and control group. (p<0.001 for all comparisons). All studied coagulation parameters were within normal limit in CH group. However, statistically significant difference was found in protein C and mean platelet count in CH group compared to control (p=0.03 and p<0.001 respectively). No evidence of bleeding or thrombosis was present in study group. In cirrhosis patients severe derangement in both anti and procoagulant factors occurs. Haemostatic profile in chronic hepatitis patient remains within normal limits.

Polymorphisms of α1-antitrypsin and Interleukin-6 genes and the progression of hepatic cirrhosis in patients with a hepatitis C virus infection

Hepatitis C virus (HCV) infection represents a serious health problem. The –174 G/C mutation in the pro inflammatory cytokine interleukin-6 (IL-6) is associated with developing liver diseases. Likewise, the S and Z mutations in the serine protease inhibitor α1-antitrypsin (A1AT) are associated with pulmonary emphysema and/or liver cirrhosis. We explored the distribution of the single nucleotide polymorphisms (SNPs) of IL-6 and A1AT genes in chronic HCV-infected patients and evaluated their impact on the progression of liver cirrhosis.One hundred and fifty Egyptian HCV-infected patients together with 100 healthy controls were enrolled in this study. The patient groups were subdivided into chronic hepatitis patients (n = 85) and cirrhotic patients (n = 65). The SNP of IL-6 (–174 G/C, rs1800795), A1AT Z mutation (342 Glu/Lys, rs28929474) and A1AT S mutation (264 Glu/Val, rs17580) were determined using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.Cirrhotic patients exhibited significantly increased frequency of the A1AT S allele compared with the controls (34.6 vs. 5.0%), while the chronic hepatitis patients showed a higher frequency of the A1AT Z allele compared with the controls (14.7 vs. 2.5%). Remarkably, IL-6 (CC genotype) was detected only in the chronic hepatitis patients. Multivariate regression analysis showed that aspartate transaminase (AST) and the S alleles of A1AT, represented as SS+MS genotypes, were significantly independent predictors for development of liver cirrhosis. We concluded that inheritance of deficient S and Z alleles of the A1AT gene but not IL-6 (–174 G/C), were associated with progressive liver diseases.

The HLA-G 14-base pair deletion allele and the deletion/deletion genotype are associated with persistent HBe antigenemia in chronic hepatis B infection

Background and aims: HLA-G has well-recognized immunomodulatory properties, and this molecule is frequently expressed in the livers of hepatitis B virus (HBV)-infected patients. Because the HLA-G 14 bp-insertion/deletion polymorphism (rs371194629) has been associated with the magnitude of HLA-G expression, we evaluated this polymorphism in the recognized evolutionary forms of chronic HBV infection. Methods: We studied 196 chronic HBV-infected patients (118 HBeAg-negative chronic hepatitis, 53 HBeAg-positive chronic hepatitis and 25 inactive carriers exhibiting low levels of serum HBVDNA and persistently normal ALT levels), and 202 healthy individuals. Chronic hepatitis HLA-G typing was performed using PCR-amplified DNA hybridized with specific primers. Results: The frequencies of the insertion/deletion alleles and genotypes were very similar in patients and controls. After patient stratification according to the evolutionary form of the chronic HBV infection, the frequencies of the deletion allele (P=0.0460; OR=1.26; 95%CI=1.01–1.45) and of the deletion/deletion genotype (P=0.0356; OR=2.08; 95%CI=1.05–4.09) were overrepresented in HBeAg-positive patients when compared to HBeAg-negative patients. No differences were observed when HBV inactive carriers were compared to HBeAg-negative chronic hepatitis patients. Conclusions: Because the 14-bp deletion allele has been associated with increased HLA-G production and because HLA-G may down regulate the cytotoxic activity of TCD8 and NK cells, patients exhibiting the 14-bp deletion allele at single or double doses are at increased risk for developing chronic forms of HBV associated with persistent viremia and worse prognoses.

Functional Polymorphism in the Interleukin 6 (IL6) Gene with Respect to Depression Induced in the Course of Interferon-α and Ribavirin Treatment in Chronic Hepatitis Patients.

Interleukin (IL)-6 is a multifactorial cytokine known to be increased in patients with chronic hepatitis C (CHC) and to be predictive of depression incidence. The aim of the study was to explore the association between IL6 gene C-174G polymorphism and depressive symptom severity in the longitudinal study design following the course of pegylated interferon/ribavirin treatment in CHC patients. In our study, we included 62 CHC subjects. They were assessed using present state examination, Beck Depression Inventory (BDI) and Montgomery Åsberg Depression Rating Scale (MADRS) at weeks 0, 3, 5, 9, 13, 24 and 24 weeks after the end of treatment. The risk of depression was associated with higher baseline MADRS score and BDI score. Interestingly, when stratified by IL6 C-174G polymorphism, higher baseline depressive symptom severity measured by MADRS and BDI predicted higher risk of depression in the course of antiviral treatment only in high IL-6 producers—G allele carriers (patients with GG and CG genotypes) (p = 0.004, p = 0.00008, respectively). There is interaction between severity of baseline depressive symptoms at the beginning of antiviral therapy and IL6 gene C-174G polymorphism leading to increased risk for the development of depressive episode in CHC patients in the course of antiviral treatment.